{ "Version": 78, "Individuals": [ { "Name": "European (P-gp modified, CYP3A4 36 h)", "Seed": 17189110, "OriginData": { "CalculationMethods": [ "SurfaceAreaPlsInt_VAR1", "Body surface area - Mosteller" ], "Species": "Human", "Population": "European_ICRP_2002", "Gender": "MALE", "Age": { "Value": 30.0, "Unit": "year(s)" } }, "Parameters": [ { "Path": "AADAC|Reference concentration", "Value": 1.0, "Unit": "µmol/l" }, { "Path": "AADAC|Relative expression in blood cells", "Value": 3.9102564103E-05 }, { "Path": "AADAC|Relative expression in plasma", "Value": 3.9102564103E-05 }, { "Path": "AADAC|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "AADAC|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "ATP1A2|Reference concentration", "Value": 0.39140774, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "ATP1A2|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "ATP1A2|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "CYP3A4|Reference concentration", "Value": 4.32, "Unit": "µmol/l" }, { "Path": "CYP3A4|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "CYP3A4|t1/2 (liver)", "Value": 36.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "GABRG2|Reference concentration", "Value": 1.04099689, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "GABRG2|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "GABRG2|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "OATP1B1|Reference concentration", "Value": 1.0, "Unit": "µmol/l" }, { "Path": "OATP1B1|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "OATP1B1|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "Organism|Bone|Intracellular|AADAC|Relative expression", "Value": 4.8717948718E-05 }, { "Path": "Organism|Bone|Intracellular|ATP1A2|Relative expression", "Value": 0.0062154033171 }, { "Path": "Organism|Bone|Intracellular|P-gp|Relative expression", "Value": 0.0242518189 }, { "Path": "Organism|Brain|Intracellular|AADAC|Relative expression", "Value": 3.9743589744E-05 }, { "Path": "Organism|Brain|Intracellular|ATP1A2|Relative expression", "Value": 1.0 }, { "Path": "Organism|Brain|Intracellular|CYP3A4|Relative expression", "Value": 0.0041682898325 }, { "Path": "Organism|Brain|Intracellular|GABRG2|Relative expression", "Value": 1.0 }, { "Path": "Organism|Brain|Intracellular|OATP1B1|Relative expression", "Value": 0.00014166666667 }, { "Path": "Organism|Brain|Intracellular|P-gp|Relative expression", "Value": 0.07608904 }, { "Path": "Organism|Gonads|Intracellular|AADAC|Relative expression", "Value": 0.0011923076923 }, { "Path": "Organism|Gonads|Intracellular|ATP1A2|Relative expression", "Value": 0.0508741242 }, { "Path": "Organism|Gonads|Intracellular|CYP3A4|Relative expression", "Value": 0.00078691079081 }, { "Path": "Organism|Gonads|Intracellular|OATP1B1|Relative expression", "Value": 0.0141666667 }, { "Path": "Organism|Gonads|Intracellular|P-gp|Relative expression", "Value": 0.017417973 }, { "Path": "Organism|Heart|Intracellular|AADAC|Relative expression", "Value": 0.0026602564103 }, { "Path": "Organism|Heart|Intracellular|ATP1A2|Relative expression", "Value": 0.3179118843 }, { "Path": "Organism|Heart|Intracellular|OATP1B1|Relative expression", "Value": 0.0008253968254 }, { "Path": "Organism|Heart|Intracellular|P-gp|Relative expression", "Value": 0.0419198106 }, { "Path": "Organism|Kidney|Intracellular|AADAC|Relative expression", "Value": 5.7051282051E-05 }, { "Path": "Organism|Kidney|Intracellular|ATP1A2|Relative expression", "Value": 0.0158938619 }, { "Path": "Organism|Kidney|Intracellular|CYP3A4|Relative expression", "Value": 0.0053603428126 }, { "Path": "Organism|Kidney|Intracellular|P-gp|Relative expression", "Value": 0.7092198582 }, { "Path": "Organism|LargeIntestine|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Intracellular|P-gp|Relative expression", "Value": 0.1108416465 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|Liver|EHC continuous fraction", "Value": 1.0, "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Organism|Liver|Pericentral|Intracellular|AADAC|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Pericentral|Intracellular|ATP1A2|Relative expression", "Value": 0.0223784807 }, { "Path": "Organism|Liver|Pericentral|Intracellular|CYP3A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Pericentral|Intracellular|OATP1B1|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Pericentral|Intracellular|P-gp|Relative expression", "Value": 0.1916810428 }, { "Path": "Organism|Liver|Pericentral|Intracellular|UGT1A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|AADAC|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|ATP1A2|Relative expression", "Value": 0.0223784807 }, { "Path": "Organism|Liver|Periportal|Intracellular|CYP3A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|OATP1B1|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|P-gp|Relative expression", "Value": 0.1916810428 }, { "Path": "Organism|Liver|Periportal|Intracellular|UGT1A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Lung|Intracellular|AADAC|Relative expression", "Value": 0.0269230769 }, { "Path": "Organism|Lung|Intracellular|ATP1A2|Relative expression", "Value": 0.0272345453 }, { "Path": "Organism|Lung|Intracellular|CYP3A4|Relative expression", "Value": 0.00042695753798 }, { "Path": "Organism|Lung|Intracellular|OATP1B1|Relative expression", "Value": 4.0079365079E-05 }, { "Path": "Organism|Lung|Intracellular|P-gp|Relative expression", "Value": 0.0657549316 }, { "Path": "Organism|Muscle|Intracellular|AADAC|Relative expression", "Value": 0.00020833333333 }, { "Path": "Organism|Muscle|Intracellular|ATP1A2|Relative expression", "Value": 0.7034193524 }, { "Path": "Organism|Muscle|Intracellular|OATP1B1|Relative expression", "Value": 0.00064682539683 }, { "Path": "Organism|Muscle|Intracellular|P-gp|Relative expression", "Value": 0.0128342959 }, { "Path": "Organism|Pancreas|Intracellular|AADAC|Relative expression", "Value": 0.1474358974 }, { "Path": "Organism|Pancreas|Intracellular|ATP1A2|Relative expression", "Value": 0.0073903254795 }, { "Path": "Organism|Pancreas|Intracellular|P-gp|Relative expression", "Value": 0.0142510689 }, { "Path": "Organism|Skin|Intracellular|ATP1A2|Relative expression", "Value": 0.0389467988 }, { "Path": "Organism|SmallIntestine|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Intracellular|P-gp|Relative expression", "Value": 0.2808543974 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|Spleen|Intracellular|AADAC|Relative expression", "Value": 0.00037115384615 }, { "Path": "Organism|Spleen|Intracellular|ATP1A2|Relative expression", "Value": 0.0103243118 }, { "Path": "Organism|Spleen|Intracellular|P-gp|Relative expression", "Value": 0.0742555691 }, { "Path": "Organism|Stomach|Intracellular|AADAC|Relative expression", "Value": 0.0775641026 }, { "Path": "Organism|Stomach|Intracellular|ATP1A2|Relative expression", "Value": 0.0309435884 }, { "Path": "Organism|Stomach|Intracellular|P-gp|Relative expression", "Value": 0.0260852897 }, { "Path": "P-gp|Reference concentration", "Value": 1.41, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "P-gp|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "P-gp|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "UGT1A4|Reference concentration", "Value": 2.32, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "UGT1A4|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "UGT1A4|t1/2 (liver)", "Value": 36.0, "Unit": "h" } ], "Molecules": [ { "Name": "CYP3A4", "Type": "Enzyme", "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome", "Ontogeny": { "Name": "CYP3A4" } }, { "Name": "AADAC", "Type": "Enzyme", "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome" }, { "Name": "P-gp", "Type": "Transporter", "TransportType": "Efflux", "Expression": [ { "Name": "Bone", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Brain", "TransportDirection": "EffluxBrainInterstitialToPlasma", "CompartmentName": "Plasma" }, { "Name": "Brain", "TransportDirection": "EffluxBrainTissueToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Fat", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Gonads", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Heart", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Kidney", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Kidney", "TransportDirection": "ExcretionKidney", "CompartmentName": "Intracellular" }, { "Name": "Stomach", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "SmallIntestine", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Duodenum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Duodenum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "UpperJejunum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "UpperJejunum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "LowerJejunum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "LowerJejunum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "UpperIleum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "UpperIleum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "LowerIleum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "LowerIleum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "LargeIntestine", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Caecum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Caecum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonAscendens", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonAscendens", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonTransversum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonTransversum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonDescendens", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonDescendens", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonSigmoid", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonSigmoid", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "Rectum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Rectum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "Periportal", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Periportal", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Pericentral", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Pericentral", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Lung", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Muscle", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Pancreas", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Skin", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Spleen", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "BloodCells", "TransportDirection": "EffluxBloodCellsToPlasma" }, { "Name": "VascularEndothelium", "TransportDirection": "EffluxInterstitialToPlasma" } ], "Ontogeny": { "Name": "P-gp", "Table": { "Name": "TableFormula", "Percentile": 0.0, "DistributionMetaData": [ { "Mean": 1E-14, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 1.915059E-05, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 5.486795E-05, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.0001571905, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.0004502473, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.001288958, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.00368424, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.01048397, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.02946235, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.0800178, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.1994918, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.4165768, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.6716791, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.8542612, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.943803, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9796414, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.992799, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9974749, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9991173, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9996917, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9998924, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9999624, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9999869, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 1.0, "Deviation": 1.6, "Distribution": "LogNormal" } ], "XName": "Postmenstrual age", "XDimension": "Age in years", "XUnit": "year(s)", "YName": "P-gp", "YDimension": "Fraction", "UseDerivedValues": false, "Points": [ { "X": 0.0, "Y": 1E-14, "RestartSolver": false }, { "X": 0.08333334, "Y": 1.915059E-05, "RestartSolver": false }, { "X": 0.1666667, "Y": 5.486795E-05, "RestartSolver": false }, { "X": 0.25, "Y": 0.0001571905, "RestartSolver": false }, { "X": 0.3333333, "Y": 0.0004502473, "RestartSolver": false }, { "X": 0.4166667, "Y": 0.001288958, "RestartSolver": false }, { "X": 0.5, "Y": 0.00368424, "RestartSolver": false }, { "X": 0.5833333, "Y": 0.01048397, "RestartSolver": false }, { "X": 0.6666667, "Y": 0.02946235, "RestartSolver": false }, { "X": 0.75, "Y": 0.0800178, "RestartSolver": false }, { "X": 0.8333333, "Y": 0.1994918, "RestartSolver": false }, { "X": 0.9166667, "Y": 0.4165768, "RestartSolver": false }, { "X": 1.0, "Y": 0.6716791, "RestartSolver": false }, { "X": 1.083333, "Y": 0.8542612, "RestartSolver": false }, { "X": 1.166667, "Y": 0.943803, "RestartSolver": false }, { "X": 1.25, "Y": 0.9796414, "RestartSolver": false }, { "X": 1.333333, "Y": 0.992799, "RestartSolver": false }, { "X": 1.416667, "Y": 0.9974749, "RestartSolver": false }, { "X": 1.5, "Y": 0.9991173, "RestartSolver": false }, { "X": 1.583333, "Y": 0.9996917, "RestartSolver": false }, { "X": 1.666667, "Y": 0.9998924, "RestartSolver": false }, { "X": 1.75, "Y": 0.9999624, "RestartSolver": false }, { "X": 1.833333, "Y": 0.9999869, "RestartSolver": false }, { "X": 3.333333, "Y": 1.0, "RestartSolver": false } ] } } }, { "Name": "OATP1B1", "Type": "Transporter", "TransportType": "Influx", "Expression": [ { "Name": "Bone", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Brain", "TransportDirection": "InfluxBrainPlasmaToInterstitial", "CompartmentName": "Plasma" }, { "Name": "Brain", "TransportDirection": "InfluxBrainInterstitialToTissue", "CompartmentName": "Interstitial" }, { "Name": "Fat", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Gonads", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Heart", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Kidney", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Kidney", "TransportDirection": "ExcretionKidney", "CompartmentName": "Intracellular" }, { "Name": "Stomach", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "SmallIntestine", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Duodenum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Duodenum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "UpperJejunum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "UpperJejunum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "LowerJejunum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "LowerJejunum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "UpperIleum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "UpperIleum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "LowerIleum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "LowerIleum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "LargeIntestine", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Caecum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Caecum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonAscendens", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonAscendens", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonTransversum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonTransversum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonDescendens", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonDescendens", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonSigmoid", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonSigmoid", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Rectum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Rectum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Periportal", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Periportal", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Pericentral", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Pericentral", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Lung", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Muscle", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Pancreas", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Skin", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Spleen", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "BloodCells", "TransportDirection": "InfluxPlasmaToBloodCells" }, { "Name": "VascularEndothelium", "TransportDirection": "InfluxPlasmaToInterstitial" } ] }, { "Name": "ATP1A2", "Type": "OtherProtein", "Localization": "Interstitial, BloodCellsMembrane, VascMembranePlasmaSide" }, { "Name": "UGT1A4", "Type": "Enzyme", "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome", "Ontogeny": { "Name": "UGT1A4" } }, { "Name": "GABRG2", "Type": "OtherProtein", "Localization": "Interstitial, BloodCellsMembrane, VascMembranePlasmaSide" } ] }, { "Name": "Korean (Yu 2004 study)", "Seed": 52995890, "OriginData": { "CalculationMethods": [ "SurfaceAreaPlsInt_VAR1", "Body surface area - Mosteller" ], "Species": "Human", "Population": "Asian_Tanaka_1996", "Gender": "MALE", "Age": { "Value": 23.3, "Unit": "year(s)" }, "Weight": { "Value": 66.9, "Unit": "kg" }, "Height": { "Value": 172.9, "Unit": "cm" } }, "Parameters": [ { "Path": "AADAC|Reference concentration", "Value": 1.0, "Unit": "µmol/l" }, { "Path": "AADAC|Relative expression in blood cells", "Value": 3.9102564103E-05 }, { "Path": "AADAC|Relative expression in plasma", "Value": 3.9102564103E-05 }, { "Path": "AADAC|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "AADAC|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "ATP1A2|Reference concentration", "Value":0.39140774, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "ATP1A2|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "ATP1A2|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "CYP3A4|Reference concentration", "Value": 3.6271334069, "Unit": "µmol/l", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Korean (Yu 2004 study)' on 2020-03-26 11:40" } }, { "Path": "CYP3A4|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "CYP3A4|t1/2 (liver)", "Value": 36.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "GABRG2|Reference concentration", "Value": 1.04099689, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "GABRG2|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "GABRG2|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "OATP1B1|Reference concentration", "Value": 1.0, "Unit": "µmol/l" }, { "Path": "OATP1B1|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "OATP1B1|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "Organism|Bone|Intracellular|AADAC|Relative expression", "Value": 4.8717948718E-05 }, { "Path": "Organism|Bone|Intracellular|ATP1A2|Relative expression", "Value": 0.0062154033171 }, { "Path": "Organism|Bone|Intracellular|P-gp|Relative expression", "Value": 0.0242518189 }, { "Path": "Organism|Brain|Intracellular|AADAC|Relative expression", "Value": 3.9743589744E-05 }, { "Path": "Organism|Brain|Intracellular|ATP1A2|Relative expression", "Value": 1.0 }, { "Path": "Organism|Brain|Intracellular|CYP3A4|Relative expression", "Value": 0.0041682898325 }, { "Path": "Organism|Brain|Intracellular|GABRG2|Relative expression", "Value": 1.0 }, { "Path": "Organism|Brain|Intracellular|OATP1B1|Relative expression", "Value": 0.00014166666667 }, { "Path": "Organism|Brain|Intracellular|P-gp|Relative expression", "Value": 0.07608904 }, { "Path": "Organism|Gonads|Intracellular|AADAC|Relative expression", "Value": 0.0011923076923 }, { "Path": "Organism|Gonads|Intracellular|ATP1A2|Relative expression", "Value": 0.0508741242 }, { "Path": "Organism|Gonads|Intracellular|CYP3A4|Relative expression", "Value": 0.00078691079081 }, { "Path": "Organism|Gonads|Intracellular|OATP1B1|Relative expression", "Value": 0.0141666667 }, { "Path": "Organism|Gonads|Intracellular|P-gp|Relative expression", "Value": 0.017417973 }, { "Path": "Organism|Heart|Intracellular|AADAC|Relative expression", "Value": 0.0026602564103 }, { "Path": "Organism|Heart|Intracellular|ATP1A2|Relative expression", "Value": 0.3179118843 }, { "Path": "Organism|Heart|Intracellular|OATP1B1|Relative expression", "Value": 0.0008253968254 }, { "Path": "Organism|Heart|Intracellular|P-gp|Relative expression", "Value": 0.0419198106 }, { "Path": "Organism|Kidney|Intracellular|AADAC|Relative expression", "Value": 5.7051282051E-05 }, { "Path": "Organism|Kidney|Intracellular|ATP1A2|Relative expression", "Value": 0.0158938619 }, { "Path": "Organism|Kidney|Intracellular|CYP3A4|Relative expression", "Value": 0.0053603428126 }, { "Path": "Organism|Kidney|Intracellular|P-gp|Relative expression", "Value": 0.7092198582 }, { "Path": "Organism|LargeIntestine|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Intracellular|P-gp|Relative expression", "Value": 0.1108416465 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|Liver|EHC continuous fraction", "Value": 1.0, "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Organism|Liver|Pericentral|Intracellular|AADAC|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Pericentral|Intracellular|ATP1A2|Relative expression", "Value": 0.0223784807 }, { "Path": "Organism|Liver|Pericentral|Intracellular|CYP3A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Pericentral|Intracellular|OATP1B1|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Pericentral|Intracellular|P-gp|Relative expression", "Value": 0.1916810428 }, { "Path": "Organism|Liver|Pericentral|Intracellular|UGT1A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|AADAC|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|ATP1A2|Relative expression", "Value": 0.0223784807 }, { "Path": "Organism|Liver|Periportal|Intracellular|CYP3A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|OATP1B1|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|P-gp|Relative expression", "Value": 0.1916810428 }, { "Path": "Organism|Liver|Periportal|Intracellular|UGT1A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Lung|Intracellular|AADAC|Relative expression", "Value": 0.0269230769 }, { "Path": "Organism|Lung|Intracellular|ATP1A2|Relative expression", "Value": 0.0272345453 }, { "Path": "Organism|Lung|Intracellular|CYP3A4|Relative expression", "Value": 0.00042695753798 }, { "Path": "Organism|Lung|Intracellular|OATP1B1|Relative expression", "Value": 4.0079365079E-05 }, { "Path": "Organism|Lung|Intracellular|P-gp|Relative expression", "Value": 0.0657549316 }, { "Path": "Organism|Muscle|Intracellular|AADAC|Relative expression", "Value": 0.00020833333333 }, { "Path": "Organism|Muscle|Intracellular|ATP1A2|Relative expression", "Value": 0.7034193524 }, { "Path": "Organism|Muscle|Intracellular|OATP1B1|Relative expression", "Value": 0.00064682539683 }, { "Path": "Organism|Muscle|Intracellular|P-gp|Relative expression", "Value": 0.0128342959 }, { "Path": "Organism|Pancreas|Intracellular|AADAC|Relative expression", "Value": 0.1474358974 }, { "Path": "Organism|Pancreas|Intracellular|ATP1A2|Relative expression", "Value": 0.0073903254795 }, { "Path": "Organism|Pancreas|Intracellular|P-gp|Relative expression", "Value": 0.0142510689 }, { "Path": "Organism|Skin|Intracellular|ATP1A2|Relative expression", "Value": 0.0389467988 }, { "Path": "Organism|SmallIntestine|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Intracellular|P-gp|Relative expression", "Value": 0.2808543974 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|Spleen|Intracellular|AADAC|Relative expression", "Value": 0.00037115384615 }, { "Path": "Organism|Spleen|Intracellular|ATP1A2|Relative expression", "Value": 0.0103243118 }, { "Path": "Organism|Spleen|Intracellular|P-gp|Relative expression", "Value": 0.0742555691 }, { "Path": "Organism|Stomach|Intracellular|AADAC|Relative expression", "Value": 0.0775641026 }, { "Path": "Organism|Stomach|Intracellular|ATP1A2|Relative expression", "Value": 0.0309435884 }, { "Path": "Organism|Stomach|Intracellular|P-gp|Relative expression", "Value": 0.0260852897 }, { "Path": "P-gp|Reference concentration", "Value": 1.41, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "P-gp|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "P-gp|t1/2 (liver)", "Value": 36.0, "Unit": "h" }, { "Path": "UGT1A4|Reference concentration", "Value": 2.32, "Unit": "µmol/l", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "UGT1A4|t1/2 (intestine)", "Value": 23.0, "Unit": "h" }, { "Path": "UGT1A4|t1/2 (liver)", "Value": 36.0, "Unit": "h" } ], "Molecules": [ { "Name": "CYP3A4", "Type": "Enzyme", "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome", "Ontogeny": { "Name": "CYP3A4" } }, { "Name": "AADAC", "Type": "Enzyme", "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome" }, { "Name": "P-gp", "Type": "Transporter", "TransportType": "Efflux", "Expression": [ { "Name": "Bone", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Brain", "TransportDirection": "EffluxBrainInterstitialToPlasma", "CompartmentName": "Plasma" }, { "Name": "Brain", "TransportDirection": "EffluxBrainTissueToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Fat", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Gonads", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Heart", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Kidney", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Kidney", "TransportDirection": "ExcretionKidney", "CompartmentName": "Intracellular" }, { "Name": "Stomach", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "SmallIntestine", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Duodenum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Duodenum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "UpperJejunum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "UpperJejunum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "LowerJejunum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "LowerJejunum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "UpperIleum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "UpperIleum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "LowerIleum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "LowerIleum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "LargeIntestine", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Caecum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Caecum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonAscendens", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonAscendens", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonTransversum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonTransversum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonDescendens", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonDescendens", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "ColonSigmoid", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "ColonSigmoid", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "Rectum", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Rectum", "TransportDirection": "EffluxMucosaIntracellularToLumen", "CompartmentName": "Intracellular" }, { "Name": "Periportal", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Periportal", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Pericentral", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Interstitial" }, { "Name": "Pericentral", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Lung", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Muscle", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Pancreas", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Skin", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "Spleen", "TransportDirection": "EffluxIntracellularToInterstitial", "CompartmentName": "Intracellular" }, { "Name": "BloodCells", "TransportDirection": "EffluxBloodCellsToPlasma" }, { "Name": "VascularEndothelium", "TransportDirection": "EffluxInterstitialToPlasma" } ], "Ontogeny": { "Name": "P-gp", "Table": { "Name": "TableFormula", "Percentile": 0.0, "DistributionMetaData": [ { "Mean": 1E-14, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 1.915059E-05, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 5.486795E-05, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.0001571905, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.0004502473, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.001288958, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.00368424, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.01048397, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.02946235, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.0800178, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.1994918, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.4165768, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.6716791, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.8542612, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.943803, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9796414, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.992799, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9974749, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9991173, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9996917, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9998924, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9999624, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 0.9999869, "Deviation": 1.6, "Distribution": "LogNormal" }, { "Mean": 1.0, "Deviation": 1.6, "Distribution": "LogNormal" } ], "XName": "Postmenstrual age", "XDimension": "Age in years", "XUnit": "year(s)", "YName": "P-gp", "YDimension": "Fraction", "UseDerivedValues": false, "Points": [ { "X": 0.0, "Y": 1E-14, "RestartSolver": false }, { "X": 0.08333334, "Y": 1.915059E-05, "RestartSolver": false }, { "X": 0.1666667, "Y": 5.486795E-05, "RestartSolver": false }, { "X": 0.25, "Y": 0.0001571905, "RestartSolver": false }, { "X": 0.3333333, "Y": 0.0004502473, "RestartSolver": false }, { "X": 0.4166667, "Y": 0.001288958, "RestartSolver": false }, { "X": 0.5, "Y": 0.00368424, "RestartSolver": false }, { "X": 0.5833333, "Y": 0.01048397, "RestartSolver": false }, { "X": 0.6666667, "Y": 0.02946235, "RestartSolver": false }, { "X": 0.75, "Y": 0.0800178, "RestartSolver": false }, { "X": 0.8333333, "Y": 0.1994918, "RestartSolver": false }, { "X": 0.9166667, "Y": 0.4165768, "RestartSolver": false }, { "X": 1.0, "Y": 0.6716791, "RestartSolver": false }, { "X": 1.083333, "Y": 0.8542612, "RestartSolver": false }, { "X": 1.166667, "Y": 0.943803, "RestartSolver": false }, { "X": 1.25, "Y": 0.9796414, "RestartSolver": false }, { "X": 1.333333, "Y": 0.992799, "RestartSolver": false }, { "X": 1.416667, "Y": 0.9974749, "RestartSolver": false }, { "X": 1.5, "Y": 0.9991173, "RestartSolver": false }, { "X": 1.583333, "Y": 0.9996917, "RestartSolver": false }, { "X": 1.666667, "Y": 0.9998924, "RestartSolver": false }, { "X": 1.75, "Y": 0.9999624, "RestartSolver": false }, { "X": 1.833333, "Y": 0.9999869, "RestartSolver": false }, { "X": 3.333333, "Y": 1.0, "RestartSolver": false } ] } } }, { "Name": "OATP1B1", "Type": "Transporter", "TransportType": "Influx", "Expression": [ { "Name": "Bone", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Brain", "TransportDirection": "InfluxBrainPlasmaToInterstitial", "CompartmentName": "Plasma" }, { "Name": "Brain", "TransportDirection": "InfluxBrainInterstitialToTissue", "CompartmentName": "Interstitial" }, { "Name": "Fat", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Gonads", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Heart", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Kidney", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Kidney", "TransportDirection": "ExcretionKidney", "CompartmentName": "Intracellular" }, { "Name": "Stomach", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "SmallIntestine", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Duodenum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Duodenum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "UpperJejunum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "UpperJejunum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "LowerJejunum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "LowerJejunum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "UpperIleum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "UpperIleum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "LowerIleum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "LowerIleum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "LargeIntestine", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Caecum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Caecum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonAscendens", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonAscendens", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonTransversum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonTransversum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonDescendens", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonDescendens", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "ColonSigmoid", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "ColonSigmoid", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Rectum", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Rectum", "TransportDirection": "InfluxLumenToMucosaIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Periportal", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Periportal", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Pericentral", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Interstitial" }, { "Name": "Pericentral", "TransportDirection": "ExcretionLiver", "CompartmentName": "Intracellular" }, { "Name": "Lung", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Muscle", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Pancreas", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Skin", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "Spleen", "TransportDirection": "InfluxInterstitialToIntracellular", "CompartmentName": "Intracellular" }, { "Name": "BloodCells", "TransportDirection": "InfluxPlasmaToBloodCells" }, { "Name": "VascularEndothelium", "TransportDirection": "InfluxPlasmaToInterstitial" } ] }, { "Name": "ATP1A2", "Type": "OtherProtein", "Localization": "Interstitial, BloodCellsMembrane, VascMembranePlasmaSide" }, { "Name": "UGT1A4", "Type": "Enzyme", "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome", "Ontogeny": { "Name": "UGT1A4" } }, { "Name": "GABRG2", "Type": "OtherProtein", "Localization": "Interstitial, BloodCellsMembrane, VascMembranePlasmaSide" } ] } ], "Compounds": [ { "Name": "Midazolam", "IsSmallMolecule": true, "PlasmaProteinBindingPartner": "Albumin", "Lipophilicity": [ { "Name": "Optimized", "Parameters": [ { "Name": "Lipophilicity", "Value": 2.8972038771, "Unit": "Log Units", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ] } ], "FractionUnbound": [ { "Name": "Gertz et al. 2010", "Species": "Human", "Parameters": [ { "Name": "Fraction unbound (plasma, reference value)", "Value": 0.031, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ] } ], "Solubility": [ { "Name": "Aqueous solubility", "IsDefault": false, "Parameters": [ { "Name": "Solubility at reference pH", "Value": 0.13, "Unit": "mg/ml", "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Heikkinen 2012" } }, { "Name": "Reference pH", "Value": 5.0, "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Heikkinen 2012" } } ] }, { "Name": "FaSSIF", "Parameters": [ { "Name": "Solubility at reference pH", "Value": 0.049, "Unit": "mg/ml", "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Heikkinen 2012" } }, { "Name": "Reference pH", "Value": 6.5, "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Heikkinen 2012" } } ] }, { "Name": "FeSSIF", "IsDefault": false, "Parameters": [ { "Name": "Solubility at reference pH", "Value": 0.09, "Unit": "mg/ml", "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Heikkinen 2012" } }, { "Name": "Reference pH", "Value": 5.0, "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Heikkinen 2012" } } ] } ], "IntestinalPermeability": [ { "Name": "Optimized", "Parameters": [ { "Name": "Specific intestinal permeability (transcellular)", "Value": 0.00015549970673, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ] } ], "PkaTypes": [ { "Type": "Base", "Pka": 6.2 }, { "Type": "Acid", "Pka": 10.95 } ], "Processes": [ { "InternalName": "SpecificBinding", "DataSource": "Buhr 1997", "Molecule": "GABRG2", "Parameters": [ { "Name": "koff", "Value": 1.0, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Name": "Kd", "Value": 1.8, "Unit": "nmol/l" } ] }, { "InternalName": "GlomerularFiltration", "DataSource": "Optimized", "Species": "Human", "Parameters": [ { "Name": "GFR fraction", "Value": 0.6401025724, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ] }, { "InternalName": "MetabolizationLiverMicrosomes_MM", "DataSource": "Optimized", "Molecule": "CYP3A4", "Parameters": [ { "Name": "In vitro Vmax for liver microsomes", "Value": 850.0, "Unit": "pmol/min/mg mic. protein" }, { "Name": "Km", "Value": 4.0, "Unit": "µmol/l", "ValueOrigin": { "Source": "Other", "Method": "InVitro", "Description": "aggregated from literature" } }, { "Name": "kcat", "Value": 8.7607941215, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ] }, { "InternalName": "MetabolizationLiverMicrosomes_MM", "DataSource": "Optimized", "Molecule": "UGT1A4", "Parameters": [ { "Name": "In vitro Vmax for liver microsomes", "Value": 276.0, "Unit": "pmol/min/mg mic. protein", "ValueOrigin": { "Source": "Publication", "Description": "Klieber 2008" } }, { "Name": "Content of CYP proteins in liver microsomes", "Value": 58.0, "Unit": "pmol/mg mic. protein", "ValueOrigin": { "Source": "Publication", "Description": "Achour 2014" } }, { "Name": "Km", "Value": 37.8, "Unit": "µmol/l", "ValueOrigin": { "Source": "Publication", "Description": "Klieber 2008" } }, { "Name": "kcat", "Value": 3.5911771641, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ] } ], "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Parameters": [ { "Name": "Cl", "Value": 1.0 }, { "Name": "F", "Value": 1.0 }, { "Name": "Molecular weight", "Value": 325.78, "Unit": "g/mol" } ] } ], "Formulations": [ { "Name": "Oral solution", "FormulationType": "Formulation_Dissolved" }, { "Name": "Tablet (Dormicum)", "FormulationType": "Formulation_Tablet_Weibull", "Parameters": [ { "Name": "Dissolution time (50% dissolved)", "Value": 0.0107481462, "Unit": "min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Tablet 7.5 mg' on 2019-04-09 16:30" } }, { "Name": "Lag time", "Value": 0.0, "Unit": "min" }, { "Name": "Dissolution shape", "Value": 4.3802943225, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Tablet 7.5 mg' on 2019-04-09 16:30" } }, { "Name": "Use as suspension", "Value": 1.0 } ] } ], "Protocols": [ { "Name": "iv 0.075 mg/kg (1 min)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.075, "Unit": "mg/kg" }, { "Name": "Infusion time", "Value": 1.0, "Unit": "min" } ] }, { "Name": "iv 0.05 mg/kg (30 min)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.05, "Unit": "mg/kg" }, { "Name": "Infusion time", "Value": 30.0, "Unit": "min" } ] }, { "Name": "iv 1 mg (5 min)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 1.0, "Unit": "mg" }, { "Name": "Infusion time", "Value": 5.0, "Unit": "min" } ] }, { "Name": "iv 0.001 mg (5 min)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.001, "Unit": "mg" }, { "Name": "Infusion time", "Value": 5.0, "Unit": "min" } ] }, { "Name": "iv 1 mg (bolus)", "ApplicationType": "IntravenousBolus", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 1.0, "Unit": "mg" } ] }, { "Name": "iv 2 mg (2 min)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 2.0, "Unit": "mg" }, { "Name": "Infusion time", "Value": 2.0, "Unit": "min" } ] }, { "Name": "iv 2 mg (bolus)", "ApplicationType": "IntravenousBolus", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 2.0, "Unit": "mg" } ] }, { "Name": "iv 0.05 mg/kg (2 min)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.05, "Unit": "mg/kg" }, { "Name": "Infusion time", "Value": 2.0, "Unit": "min" } ] }, { "Name": "iv 5 mg (30 sec)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 5.0, "Unit": "mg" }, { "Name": "Infusion time", "Value": 30.0, "Unit": "s" } ] }, { "Name": "iv 5 mg (bolus)", "ApplicationType": "IntravenousBolus", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 5.0, "Unit": "mg" } ] }, { "Name": "iv 0.05 mg/kg (bolus)", "ApplicationType": "IntravenousBolus", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.05, "Unit": "mg/kg" } ] }, { "Name": "iv 0.15 mg/kg (bolus)", "ApplicationType": "IntravenousBolus", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.15, "Unit": "mg/kg" } ] }, { "Name": "po 1 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 1.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 5 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 5.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 7.5 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 7.5, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 0.075 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.075, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 3 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 3.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 4 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 4.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 6 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 6.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 8 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 8.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 15 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 15.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 2 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 2.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 0.075 mg/kg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.075, "Unit": "mg/kg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 10 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 10.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 20 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 20.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 40 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 40.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 0.003 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.003, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 15 mg (1 h delayed)", "DosingInterval": "Single", "Schemas": [ { "Name": "Schema 1", "SchemaItems": [ { "Name": "Schema Item 1", "ApplicationType": "Oral", "FormulationKey": "Formulation", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 15.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] } ], "Parameters": [ { "Name": "Start time", "Value": 1.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "NumberOfRepetitions", "Value": 1.0 }, { "Name": "TimeBetweenRepetitions", "Value": 0.0, "Unit": "h" } ] } ], "TimeUnit": "h" }, { "Name": "po 2.5 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 2.5, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 0.01 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 0.01, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "po 3.5 mg", "ApplicationType": "Oral", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 3.5, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] }, { "Name": "Mikus 2017", "DosingInterval": "Single", "Schemas": [ { "Name": "Schema 1", "SchemaItems": [ { "Name": "Schema Item 1", "ApplicationType": "Intravenous", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 2.0, "Unit": "mg" }, { "Name": "Infusion time", "Value": 30.0, "Unit": "min" } ] } ], "Parameters": [ { "Name": "Start time", "Value": 6.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "NumberOfRepetitions", "Value": 1.0 }, { "Name": "TimeBetweenRepetitions", "Value": 0.0, "Unit": "h" } ] }, { "Name": "Schema 2", "SchemaItems": [ { "Name": "Schema Item 1", "ApplicationType": "Oral", "FormulationKey": "Formulation", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 4.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] } ], "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "NumberOfRepetitions", "Value": 1.0 }, { "Name": "TimeBetweenRepetitions", "Value": 0.0, "Unit": "h" } ] } ], "TimeUnit": "h" }, { "Name": "iv 1 mg (2 min)", "ApplicationType": "Intravenous", "DosingInterval": "Single", "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "InputDose", "Value": 1.0, "Unit": "mg" }, { "Name": "Infusion time", "Value": 2.0, "Unit": "min" } ] } ], "Events": [ { "Name": "High-fat breakfast", "Template": "Meal: High-fat breakfast (Human)" } ], "Simulations": [ { "Name": "iv 0.001 mg (5 min)", "Model": "4Comp", "ObservedData": [ "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 0.001 mg (5 min)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 5.0, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 0.001 mg (5 min)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 0.001 mg (5 min)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 0.001 mg (5 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)|Time", "Y": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 0.001 mg (5 min) - Plasma", "OriginText": "Midazolam_2.1\niv 0.001 mg (5 min)\n2018-09-28 10:55" } ] }, { "Name": "iv 0.05 mg/kg (2 min)", "Model": "4Comp", "ObservedData": [ "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)", "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)", "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 0.05 mg/kg (2 min)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 2.0, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 0.05 mg/kg (2 min)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 0.05 mg/kg (2 min)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 0.05 mg/kg (2 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)|Time", "Y": "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)|Time", "Y": "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)|Time", "Y": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 0.05 mg/kg (2 min) - Plasma", "OriginText": "Midazolam_2.3\niv 0.05 mg/kg (2 min)\n2019-04-09 17:32" } ] }, { "Name": "iv 0.05 mg/kg (30 min)", "Model": "4Comp", "ObservedData": [ "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)", "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)", "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 0.05 mg/kg (30 min)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 30.0, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 0.05 mg/kg (30 min)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 0.05 mg/kg (30 min)-Midazolam-Peripheral Venous Blood-Whole Blood-Concentration", "X": "Time", "Y": "iv 0.05 mg/kg (30 min)|Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 2 } }, { "Name": "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)-Midazolam-Peripheral Venous Blood-Whole Blood-ArithmeticMean", "X": "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)|Time", "Y": "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)-Midazolam-Peripheral Venous Blood-Whole Blood-ArithmeticMean", "X": "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|Time", "Y": "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)-Midazolam-Peripheral Venous Blood-Whole Blood-ArithmeticMean", "X": "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|Time", "Y": "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#00C000", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 0.05 mg/kg (30 min) - Whole blood", "OriginText": "Midazolam-Model\niv 0.05 mg/kg (30 min)\n2019-05-09 10:32" } ] }, { "Name": "iv 0.05 mg/kg (bolus)", "Model": "4Comp", "ObservedData": [ "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 0.05 mg/kg (bolus)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 0.05 mg/kg (bolus)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 0.05 mg/kg (bolus)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)|Time", "Y": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 0.05 mg/kg (bolus) - Plasma", "OriginText": "Midazolam_2.2\niv 0.05 mg/kg (bolus)\n2018-10-02 13:03" } ] }, { "Name": "iv 0.075 mg/kg (1 min)", "Model": "4Comp", "ObservedData": [ "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)", "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 0.075 mg/kg (1 min)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 1.0, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 0.075 mg/kg (1 min)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 0.075 mg/kg (1 min)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 0.075 mg/kg (1 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)|Time", "Y": "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)|Time", "Y": "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 0.075 mg/kg (1 min) - Plasma", "OriginText": "Midazolam_2.2\niv 0.075 mg/kg (1 min)\n2018-10-02 13:03" } ] }, { "Name": "iv 0.15 mg/kg (bolus)", "Model": "4Comp", "ObservedData": [ "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv." ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 0.15 mg/kg (bolus)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 0.15 mg/kg (bolus)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 0.15 mg/kg (bolus)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#00C0C0", "LegendIndex": 7, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 0.15 mg/kg (bolus) - Plasma", "OriginText": "Midazolam_2.2\niv 0.15 mg/kg (bolus)\n2018-10-02 13:04" } ] }, { "Name": "iv 1 mg (5 min)", "Model": "4Comp", "ObservedData": [ "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)", "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)", "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)", "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 1 mg (5 min)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 5.0, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "Organism|Kidney|Urine|Midazolam|Fraction excreted to urine" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 1 mg (5 min)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 1 mg (5 min)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 1 mg (5 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)|Time", "Y": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 1 mg (5 min) - Plasma", "OriginText": "Midazolam_2.1\niv 1 mg (5 min)\n2018-09-28 10:55" }, { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "%", "Dimension": "Fraction", "Type": "Y", "GridLines": false, "Visible": true, "Min": 0.0, "Max": 3.0, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Linear", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "iv 1 mg (5 min)-Midazolam-Kidney-Urine-Fraction excreted to urine", "X": "Time", "Y": "iv 1 mg (5 min)|Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "CurveOptions": { "LegendIndex": 3 } } ], "Name": "iv 1 mg (5 min) - Urine", "OriginText": "Midazolam-Model2\niv 1 mg (5 min)\n2019-05-10 15:26" }, { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "%", "Dimension": "Fraction", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Linear", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 1 mg (5 min)-Midazolam-UGT1A4-Optimized Metabolite-Liver Periportal-Intracellular-Fraction of dose-Midazolam", "X": "Time", "Y": "iv 1 mg (5 min)|Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)-Midazolam-N-Glucuronide-Kidney-Urine-ArithmeticMean", "X": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|Time", "Y": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 1 mg (5 min) - fm UGT1A4", "OriginText": "Midazolam-Model2\niv 1 mg (5 min)\n2019-05-10 15:26" } ] }, { "Name": "iv 1 mg (bolus)", "Model": "4Comp", "ObservedData": [ "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)", "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)", "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)", "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)", "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)", "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)", "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|Liver|Periportal|Intracellular|Midazolam-CYP3A4-Optimized Metabolite|Fraction of dose-Midazolam", "Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "Organism|Kidney|Urine|Midazolam|Fraction excreted to urine" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 1 mg (bolus)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 1 mg (bolus)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 1 mg (bolus)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|Time", "Y": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#00C0C0", "LegendIndex": 7, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)|Time", "Y": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|Time", "Y": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)|Time", "Y": "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|Time", "Y": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)|Time", "Y": "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 1 mg (bolus) - Plasma", "OriginText": "Midazolam-Model\niv 1 mg (bolus)\n2019-05-09 10:39" }, { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "%", "Dimension": "Fraction", "Type": "Y", "GridLines": false, "Visible": true, "Min": 0.0, "Max": 3.0, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Linear", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "iv 1 mg (bolus)-Midazolam-Kidney-Urine-Fraction excreted to urine", "X": "Time", "Y": "iv 1 mg (bolus)|Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "CurveOptions": { "LegendIndex": 1 } } ], "Name": "iv 1 mg (bolus) - Urine", "OriginText": "Midazolam-Model\niv 1 mg (bolus)\n2019-05-09 18:41" }, { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "%", "Dimension": "Fraction", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Linear", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 1 mg (bolus)-Midazolam-UGT1A4-Optimized Metabolite-Liver Periportal-Intracellular-Fraction of dose-Midazolam", "X": "Time", "Y": "iv 1 mg (bolus)|Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)-Midazolam-N-Glucuronide-Kidney-Urine-ArithmeticMean", "X": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|Time", "Y": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 1 mg (bolus) - fm UGT1A4", "OriginText": "Midazolam-Model\niv 1 mg (bolus)\n2019-05-09 18:41" } ] }, { "Name": "iv 2 mg (2 min)", "Model": "4Comp", "ObservedData": [ "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 2 mg (2 min)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 2.0, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 2 mg (2 min)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 2 mg (2 min)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 2 mg (2 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|Time", "Y": "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 2 mg (2 min) - Plasma", "OriginText": "Midazolam-Model\niv 2 mg (2 min)\n2019-05-09 10:52" } ] }, { "Name": "iv 2 mg (bolus)", "Model": "4Comp", "ObservedData": [ "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)", "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 2 mg (bolus)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 2 mg (bolus)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 2 mg (bolus)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)|Time", "Y": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)|Time", "Y": "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 2 mg (bolus) - Plasma", "OriginText": "Midazolam_2.2\niv 2 mg (bolus)\n2018-10-02 13:10" } ] }, { "Name": "iv 5 mg (30 sec)", "Model": "4Comp", "ObservedData": [ "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 5 mg (30 sec)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 0.5, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 5 mg (30 sec)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 5 mg (30 sec)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 5 mg (30 sec)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)|Time", "Y": "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 5 mg (30 sec) - Plasma", "OriginText": "Midazolam_2.2\niv 5 mg (30 sec)\n2018-10-02 13:11" } ] }, { "Name": "iv 5 mg (bolus)", "Model": "4Comp", "ObservedData": [ "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 5 mg (bolus)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 5 mg (bolus)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 5 mg (bolus)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)|Time", "Y": "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 5 mg (bolus) - Plasma", "OriginText": "Midazolam_2.2\niv 5 mg (bolus)\n2018-10-02 13:12" } ] }, { "Name": "po 0.003 mg (solution)", "Model": "4Comp", "ObservedData": [ "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 0.003 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 0.003 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)|Time", "Y": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "po 0.003 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 0.003 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } } ], "Name": "po 0.003 mg (solution) - Plasma", "OriginText": "Midazolam_2.1\npo 0.003 mg (solution)\n2018-09-28 10:55" } ] }, { "Name": "po 0.075 mg (solution)", "Model": "4Comp", "ObservedData": [ "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 0.075 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 0.075 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 0.075 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 0.075 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)-Midazolam-Peripheral Venous Blood-Plasma-GeometricMean", "X": "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)|Time", "Y": "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 0.075 mg (solution) - Plasma", "OriginText": "Midazolam_2.2\npo 0.075 mg (solution)\n2018-10-02 13:28" } ] }, { "Name": "po 0.075 mg/kg (syrup)", "Model": "4Comp", "ObservedData": [ "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 0.075 mg/kg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 0.075 mg/kg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 0.075 mg/kg (syrup)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 0.075 mg/kg (syrup)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 3 } }, { "Name": "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)|Time", "Y": "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 0.075 mg/kg (syrup) - Plasma", "OriginText": "Midazolam_2.2\npo 0.075 mg/kg (syrup)\n2018-10-02 13:29" } ] }, { "Name": "po 1 mg (solution)", "Model": "4Comp", "ObservedData": [ "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)", "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 1 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 1 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)-Midazolam-Peripheral Venous Blood-Plasma-Median", "X": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)|Time", "Y": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Median", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 1 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)|Time", "Y": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)-Midazolam-Peripheral Venous Blood-Plasma-GeometricMean", "X": "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|Time", "Y": "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 1 mg (solution) - Plasma", "OriginText": "Midazolam_2.3\npo 1 mg (solution)\n2019-04-09 17:38" } ] }, { "Name": "po 10 mg (tablet)", "Model": "4Comp", "ObservedData": [ "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.", "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.", "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.", "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 10 mg|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 10 mg", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 10 mg (tablet)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 10 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|Time", "Y": "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 10 mg (tablet) - Plasma", "OriginText": "Midazolam_2.2\npo 10 mg (tablet)\n2018-10-02 18:35" } ] }, { "Name": "po 15 mg (tablet)", "Model": "4Comp", "ObservedData": [ "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)", "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)", "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)", "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)", "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)", "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)", "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 15 mg|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 15 mg", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Y": "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#C000C0", "LegendIndex": 8, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)|Time", "Y": "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|Time", "Y": "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|Time", "Y": "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|Time", "Y": "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|Time", "Y": "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "po 15 mg (tablet)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 15 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)|Time", "Y": "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#00C0C0", "LegendIndex": 7, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|Time", "Y": "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#C04000", "LegendIndex": 9, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 15 mg (tablet) - Plasma", "OriginText": "Midazolam_2.2\npo 15 mg (tablet)\n2018-10-02 18:23" } ] }, { "Name": "po 2 mg (solution)", "Model": "4Comp", "ObservedData": [ "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)", "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 2 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 2 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 2 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 2 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)|Time", "Y": "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|Time", "Y": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|Time", "Y": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 2 mg (solution) - Plasma", "OriginText": "Midazolam_2.2\npo 2 mg (solution)\n2018-10-02 18:35" } ] }, { "Name": "po 20 mg (tablet)", "Model": "4Comp", "ObservedData": [ "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv." ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 20 mg|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 20 mg", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 20 mg (tablet)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 20 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#00C0C0", "LegendIndex": 7, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 20 mg (tablet) - Plasma", "OriginText": "Midazolam_2.2\npo 20 mg (tablet)\n2018-10-02 18:37" } ] }, { "Name": "po 3 mg (solution)", "Model": "4Comp", "ObservedData": [ "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)", "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)", "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)", "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)", "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)", "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)", "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 3 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)", "Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "Organism|Liver|Periportal|Intracellular|Midazolam-CYP3A4-Optimized Metabolite|Fraction of dose-Midazolam", "Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 3 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|Time", "Y": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|Time", "Y": "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)|Time", "Y": "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "po 3 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 3 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)|Time", "Y": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)|Time", "Y": "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 3 mg (solution) - Plasma", "OriginText": "Midazolam_2.3c\npo 3 mg (solution)\n2019-04-11 18:13" }, { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "%", "Dimension": "Fraction", "Type": "Y", "GridLines": false, "Visible": true, "Min": 1.017808E-05, "Max": 3.0, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Linear", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "po 3 mg (solution)-Midazolam-Kidney-Urine-Fraction excreted to urine", "X": "Time", "Y": "po 3 mg (solution)|Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "CurveOptions": { "LegendIndex": 1 } } ], "Name": "po 3 mg (solution) - Urine", "OriginText": "Midazolam-Model2\npo 3 mg (solution)\n2019-05-10 15:28" }, { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "%", "Dimension": "Fraction", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Linear", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)-Midazolam-N-Glucuronide-Kidney-Urine-ArithmeticMean", "X": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)|Time", "Y": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "po 3 mg (solution)-Midazolam-UGT1A4-Optimized Metabolite-Liver Periportal-Intracellular-Fraction of dose-Midazolam", "X": "Time", "Y": "po 3 mg (solution)|Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "CurveOptions": { "LegendIndex": 1 } } ], "Name": "po 3 mg (solution) - fm UGT1A4", "OriginText": "Midazolam-Model2\npo 3 mg (solution)\n2019-05-10 15:28" } ] }, { "Name": "po 4 mg (solution)", "Model": "4Comp", "ObservedData": [ "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)", "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 4 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 4 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 4 mg (solution)-Midazolam-Peripheral Venous Blood-Whole Blood-Concentration", "X": "Time", "Y": "po 4 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 2 } }, { "Name": "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)-Midazolam-Peripheral Venous Blood-Whole Blood-ArithmeticMean", "X": "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)|Time", "Y": "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)-Midazolam-Peripheral Venous Blood-Whole Blood-ArithmeticMean", "X": "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)|Time", "Y": "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 4 mg (solution) - Whole blood", "OriginText": "Midazolam-Model\npo 4 mg (solution)\n2019-07-25 10:54" } ] }, { "Name": "po 40 mg (tablet)", "Model": "4Comp", "ObservedData": [ "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv.", "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.", "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv." ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 40 mg|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 40 mg", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 40 mg (tablet)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 40 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv.-Midazolam-Peripheral Venous Blood-Plasma-Individual", "X": "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv.|Time", "Y": "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 40 mg (tablet) - Plasma", "OriginText": "Midazolam_2.2\npo 40 mg (tablet)\n2018-10-02 18:38" } ] }, { "Name": "po 5 mg (solution)", "Model": "4Comp", "ObservedData": [ "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)", "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)", "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 5 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 5 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 5 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 5 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)|Time", "Y": "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)|Time", "Y": "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)|Time", "Y": "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 5 mg (solution) - Plasma", "OriginText": "Midazolam_2.2\npo 5 mg (solution)\n2018-10-02 18:18" } ] }, { "Name": "po 6 mg (solution)", "Model": "4Comp", "ObservedData": [ "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 6 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 6 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 6 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 6 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 3 } }, { "Name": "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|Time", "Y": "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 6 mg (solution) - Plasma", "OriginText": "Midazolam_2.2\npo 6 mg (solution)\n2018-10-02 18:39" } ] }, { "Name": "po 7.5 mg (solution)", "Model": "4Comp", "ObservedData": [ "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 7.5 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 7.5 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 7.5 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 7.5 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)-Midazolam-Peripheral Venous Blood-Plasma-GeometricMean", "X": "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)|Time", "Y": "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 7.5 mg (solution) - Plasma", "OriginText": "Midazolam_2.2\npo 7.5 mg (solution)\n2018-10-02 18:39" } ] }, { "Name": "po 8 mg (solution)", "Model": "4Comp", "ObservedData": [ "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 8 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 8 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 8 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 8 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Y": "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#C04000", "LegendIndex": 9, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Y": "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#C000C0", "LegendIndex": 8, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Y": "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#00C0C0", "LegendIndex": 7, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Y": "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Y": "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Y": "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Y": "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Y": "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 8 mg (solution) - Plasma", "Settings": { "SideMarginsEnabled": true, "LegendPosition": "Bottom", "BackColor": "#FFFFFF", "DiagramBackColor": "#FFFFFF" }, "OriginText": "Midazolam_2.2\npo 8 mg (solution)\n2018-10-09 15:06" } ] }, { "Name": "po 7.5 mg (tablet)", "Model": "4Comp", "ObservedData": [ "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)", "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)", "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 7.5 mg|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 7.5 mg", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "Min": -0.2275229, "Max": 25.26728, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "Min": 0.09416887, "Max": 336.4494, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 7.5 mg (tablet)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 7.5 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)|Time", "Y": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#00C0C0", "LegendIndex": 7, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|Time", "Y": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|Time", "Y": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)|Time", "Y": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)|Time", "Y": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|Time", "Y": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 7.5 mg (tablet) - Plasma", "OriginText": "Midazolam-Model\npo 7.5 mg (tablet)\n2019-05-10 09:26" } ] }, { "Name": "po 10 mg (solution)", "Model": "4Comp", "ObservedData": [ "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)", "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)", "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 10 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 10 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "Min": -0.832368433, "Max": 12.6202488, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "Min": 0.248819932, "Max": 95.56502, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|Time", "Y": "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|Time", "Y": "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "po 10 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 10 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|Time", "Y": "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 10 mg (solution) - Plasma", "OriginText": "Midazolam_2.2\npo 10 mg (solution)\n2018-10-02 18:50" } ] }, { "Name": "po 15 mg (tablet) - with high-fat breakfast", "Model": "4Comp", "ObservedData": [ "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 15 mg|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 15 mg", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "Events": [ { "Name": "High-fat breakfast", "StartTime": { "Value": 0.0, "Unit": "h" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "Min": -0.1162777, "Max": 13.94921, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "Min": 0.6674016, "Max": 66.57937, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 15 mg (tablet) - with high-fat breakfast-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 15 mg (tablet) - with high-fat breakfast|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 7 } }, { "Name": "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Y": "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 9, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 15 mg (tablet) - with high-fat breakfast - Plasma", "OriginText": "Midazolam_2.2\npo 15 mg (tablet) - with high-fat breakfast\n2018-10-08 12:00" } ] }, { "Name": "po 15 mg (tablet) - with 1 h before high-fat breakfast", "Model": "4Comp", "ObservedData": [ "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 15 mg|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 15 mg", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "Events": [ { "Name": "High-fat breakfast", "StartTime": { "Value": 1.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 15 mg (tablet) - with 1 h before high-fat breakfast-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 15 mg (tablet) - with 1 h before high-fat breakfast|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 7 } }, { "Name": "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Y": "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 9, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 15 mg (tablet) - with 1 h before high-fat breakfast - Plasma", "OriginText": "Midazolam_2.2\npo 15 mg (tablet) - with 1 h before high-fat breakfast\n2018-10-08 12:00" } ] }, { "Name": "po 15 mg (tablet) - with 1h after high-fat breakfast", "Model": "4Comp", "ObservedData": [ "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 15 mg (1 h delayed)|Tablet (Dormicum)|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 15 mg (1 h delayed)", "Formulations": [ { "Name": "Tablet (Dormicum)", "Key": "Formulation" } ] } } ], "Events": [ { "Name": "High-fat breakfast", "StartTime": { "Value": 0.0, "Unit": "h" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "Min": 0.9232998, "Max": 12.83503, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "Min": 0.7475061, "Max": 43.31379, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 15 mg (tablet) - with 1h after high-fat breakfast-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 15 mg (tablet) - with 1h after high-fat breakfast|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 7 } }, { "Name": "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Y": "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 8, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 15 mg (tablet) - with 1h after high-fat breakfast - Plasma", "OriginText": "Midazolam_2.2\npo 15 mg (tablet) - with 1h after high-fat breakfast\n2018-10-08 11:59" } ] }, { "Name": "po 2.5 mg (solution)", "Model": "4Comp", "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 2.5 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 2.5 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 2.5 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 2.5 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } } ], "Name": "po 2.5 mg (solution) - Plasma", "OriginText": "Midazolam-Model\npo 2.5 mg (solution)\n2019-05-09 18:32" } ] }, { "Name": "po 3.5 mg (solution)", "Model": "4Comp", "ObservedData": [ "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 3.5 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 3.5 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 3.5 mg (solution)-Midazolam-Peripheral Venous Blood-Whole Blood-Concentration", "X": "Time", "Y": "po 3.5 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Whole Blood (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 2 } }, { "Name": "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)-Midazolam-Peripheral Venous Blood-Whole Blood-ArithmeticMean", "X": "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)|Time", "Y": "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 3.5 mg (solution) - Whole blood" } ] }, { "Name": "po 0.01 mg (solution)", "Model": "4Comp", "ObservedData": [ "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|po 0.01 mg|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "po 0.01 mg", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "po 0.01 mg (solution)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "po 0.01 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)|Time", "Y": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "po 0.01 mg (solution) - Plasma" } ] }, { "Name": "Mikus 2017", "Model": "4Comp", "ObservedData": [ "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)", "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 6.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 6.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "End time", "Value": 8.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h", "ValueOrigin": { "Source": "Unknown" } } ] }, { "Parameters": [ { "Name": "Start time", "Value": 8.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "End time", "Value": 24.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|Mikus 2017|Application_2|ProtocolSchemaItem|Infusion time", "Value": 30.0, "Unit": "min" }, { "Path": "Applications|Mikus 2017|Oral solution|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)" ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "Mikus 2017", "Formulations": [ { "Name": "Oral solution", "Key": "Formulation" } ] } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Mikus 2017-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "Mikus 2017|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)|Time", "Y": "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|Time", "Y": "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "Mikus 2017 (4 mg po followed by 2 mg iv)", "OriginText": "Midazolam-Model\nMikus 2017\n2020-03-05 12:54" } ] }, { "Name": "iv 1 mg (2 min)", "Model": "4Comp", "ObservedData": [ "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 2.0, "Unit": "h" }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h" } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h" }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|iv 1 mg (2 min)|Application_1|ProtocolSchemaItem|Infusion time", "Value": 2.0, "Unit": "min" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "Value": 0.0019242177595, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint' on 2019-04-09 16:10" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "Organism|Liver|Periportal|Intracellular|Midazolam-CYP3A4-Optimized Metabolite|Fraction of dose-Midazolam", "Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "Organism|Kidney|Urine|Midazolam|Fraction excreted to urine" ], "Individual": "Korean (Yu 2004 study)", "Compounds": [ { "Name": "Midazolam", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "FaSSIF", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Optimized", "MoleculeName": "CYP3A4" }, { "Name": "UGT1A4-Optimized", "MoleculeName": "UGT1A4" }, { "Name": "Glomerular Filtration-Optimized", "SystemicProcessType": "GFR" }, { "Name": "GABRG2-Buhr 1997", "MoleculeName": "GABRG2" } ], "Protocol": { "Name": "iv 1 mg (2 min)" } } ], "HasResults": true, "IndividualAnalyses": [ { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "ng/ml", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "iv 1 mg (2 min)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 1 mg (2 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "LegendIndex": 1 } }, { "Name": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)|Time", "Y": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "iv 1 mg (2 min) [Korean] - Plasma", "OriginText": "Midazolam-Model_v1.0\niv 1 mg (2 min)\n2020-03-26 11:39" } ] } ], "ParameterIdentifications": [ { "Name": "PI Hohmann iv+po, Hyland feUr MDZG, Thummel feUr unchanged - Pint", "Simulations": [ "po 0.003 mg (solution)", "iv 1 mg (5 min)", "iv 0.001 mg (5 min)", "po 3 mg (solution)" ], "Configuration": { "LLOQMode": "OnlyObservedData", "RemoveLLOQMode": "NoTrailing", "CalculateJacobian": true, "Algorithm": { "Name": "Levenberg - Marquardt (MPFit)", "Properties": [ { "Name": "ftol", "Value": 0.001 }, { "Name": "xtol", "Value": 1E-06 }, { "Name": "gtol", "Value": 1E-10 }, { "Name": "stepfactor", "Value": 100.0 }, { "Name": "maxiter", "Value": 200.0 }, { "Name": "maxfev", "Value": 0.0 }, { "Name": "epsfcn", "Value": 1E-09 } ] } }, "OutputMappings": [ { "Scaling": "Log", "Path": "po 3 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)" }, { "Scaling": "Log", "Path": "po 3 mg (solution)|Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "ObservedData": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)" }, { "Scaling": "Log", "Path": "po 3 mg (solution)|Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "ObservedData": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)" }, { "Scaling": "Log", "Path": "po 3 mg (solution)|Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "ObservedData": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)" }, { "Scaling": "Log", "Path": "po 0.003 mg (solution)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)" }, { "Scaling": "Log", "Path": "iv 1 mg (5 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)" }, { "Scaling": "Log", "Path": "iv 1 mg (5 min)|Organism|Liver|Periportal|Intracellular|Midazolam-UGT1A4-Optimized Metabolite|Fraction of dose-Midazolam", "ObservedData": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)" }, { "Scaling": "Log", "Path": "iv 1 mg (5 min)|Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "ObservedData": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)" }, { "Scaling": "Log", "Path": "iv 1 mg (5 min)|Organism|Kidney|Urine|Midazolam|Fraction excreted to urine", "ObservedData": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)" }, { "Scaling": "Log", "Path": "iv 0.001 mg (5 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)" } ], "IdentificationParameters": [ { "Name": "Lipophilicity", "Scaling": "Linear", "LinkedParameters": [ "po 3 mg (solution)|Midazolam|Lipophilicity", "po 0.003 mg (solution)|Midazolam|Lipophilicity", "iv 1 mg (5 min)|Midazolam|Lipophilicity", "iv 0.001 mg (5 min)|Midazolam|Lipophilicity" ], "Parameters": [ { "Name": "Start value", "Value": 3.1, "Unit": "Log Units" }, { "Name": "MinValue", "Value": 2.8, "Unit": "Log Units" }, { "Name": "MaxValue", "Value": 4.0, "Unit": "Log Units" } ] }, { "Name": "Fraction unbound (plasma, reference value)", "Scaling": "Linear", "IsFixed": true, "LinkedParameters": [ "po 3 mg (solution)|Midazolam|Fraction unbound (plasma, reference value)", "po 0.003 mg (solution)|Midazolam|Fraction unbound (plasma, reference value)", "iv 1 mg (5 min)|Midazolam|Fraction unbound (plasma, reference value)", "iv 0.001 mg (5 min)|Midazolam|Fraction unbound (plasma, reference value)" ], "Parameters": [ { "Name": "Start value", "Value": 0.031 }, { "Name": "MinValue", "Value": 0.01 }, { "Name": "MaxValue", "Value": 0.05 } ] }, { "Name": "Solubility at reference pH", "Scaling": "Linear", "IsFixed": true, "LinkedParameters": [ "po 3 mg (solution)|Midazolam|Solubility at reference pH", "po 0.003 mg (solution)|Midazolam|Solubility at reference pH", "iv 1 mg (5 min)|Midazolam|Solubility at reference pH", "iv 0.001 mg (5 min)|Midazolam|Solubility at reference pH" ], "Parameters": [ { "Name": "Start value", "Value": 0.049, "Unit": "mg/ml" }, { "Name": "MinValue", "Value": 0.0, "Unit": "mg/ml" }, { "Name": "MaxValue", "Value": 0.49, "Unit": "mg/ml" } ] }, { "Name": "Specific intestinal permeability (transcellular)", "Scaling": "Log", "LinkedParameters": [ "po 3 mg (solution)|Midazolam|Specific intestinal permeability (transcellular)", "po 0.003 mg (solution)|Midazolam|Specific intestinal permeability (transcellular)", "iv 1 mg (5 min)|Midazolam|Specific intestinal permeability (transcellular)", "iv 0.001 mg (5 min)|Midazolam|Specific intestinal permeability (transcellular)" ], "Parameters": [ { "Name": "Start value", "Value": 0.0001754, "Unit": "cm/min" }, { "Name": "MinValue", "Value": 1E-05, "Unit": "cm/min" }, { "Name": "MaxValue", "Value": 0.1, "Unit": "cm/min" } ] }, { "Name": "Km CYP3A4", "Scaling": "Linear", "IsFixed": true, "LinkedParameters": [ "po 3 mg (solution)|Midazolam-CYP3A4-Optimized|Km", "po 0.003 mg (solution)|Midazolam-CYP3A4-Optimized|Km", "iv 1 mg (5 min)|Midazolam-CYP3A4-Optimized|Km", "iv 0.001 mg (5 min)|Midazolam-CYP3A4-Optimized|Km" ], "Parameters": [ { "Name": "Start value", "Value": 4.0, "Unit": "µmol/l" }, { "Name": "MinValue", "Value": 0.1, "Unit": "µmol/l" }, { "Name": "MaxValue", "Value": 40.0, "Unit": "µmol/l" } ] }, { "Name": "kcat CYP3A4", "Scaling": "Log", "LinkedParameters": [ "po 3 mg (solution)|Midazolam-CYP3A4-Optimized|kcat", "po 0.003 mg (solution)|Midazolam-CYP3A4-Optimized|kcat", "iv 1 mg (5 min)|Midazolam-CYP3A4-Optimized|kcat", "iv 0.001 mg (5 min)|Midazolam-CYP3A4-Optimized|kcat" ], "Parameters": [ { "Name": "Start value", "Value": 7.8703703704, "Unit": "1/min" }, { "Name": "MinValue", "Value": 1.0, "Unit": "1/min" }, { "Name": "MaxValue", "Value": 20.0, "Unit": "1/min" } ] }, { "Name": "koff", "Scaling": "Linear", "IsFixed": true, "LinkedParameters": [ "po 3 mg (solution)|Midazolam-GABRG2-Buhr 1997|koff", "po 0.003 mg (solution)|Midazolam-GABRG2-Buhr 1997|koff", "iv 1 mg (5 min)|Midazolam-GABRG2-Buhr 1997|koff", "iv 0.001 mg (5 min)|Midazolam-GABRG2-Buhr 1997|koff" ], "Parameters": [ { "Name": "Start value", "Value": 1.0, "Unit": "1/min" }, { "Name": "MinValue", "Value": 0.0, "Unit": "1/min" }, { "Name": "MaxValue", "Value": 10.0, "Unit": "1/min" } ] }, { "Name": "GFR fraction", "Scaling": "Log", "LinkedParameters": [ "po 3 mg (solution)|Neighborhoods|Kidney_pls_Kidney_ur|Midazolam|Glomerular Filtration-Optimized|GFR fraction", "po 0.003 mg (solution)|Neighborhoods|Kidney_pls_Kidney_ur|Midazolam|Glomerular Filtration-Optimized|GFR fraction", "iv 1 mg (5 min)|Neighborhoods|Kidney_pls_Kidney_ur|Midazolam|Glomerular Filtration-Optimized|GFR fraction", "iv 0.001 mg (5 min)|Neighborhoods|Kidney_pls_Kidney_ur|Midazolam|Glomerular Filtration-Optimized|GFR fraction" ], "Parameters": [ { "Name": "Start value", "Value": 0.3 }, { "Name": "MinValue", "Value": 0.001 }, { "Name": "MaxValue", "Value": 2.0 } ] }, { "Name": "Km UGT1A4", "Scaling": "Linear", "IsFixed": true, "LinkedParameters": [ "po 3 mg (solution)|Midazolam-UGT1A4-Optimized|Km", "po 0.003 mg (solution)|Midazolam-UGT1A4-Optimized|Km", "iv 1 mg (5 min)|Midazolam-UGT1A4-Optimized|Km", "iv 0.001 mg (5 min)|Midazolam-UGT1A4-Optimized|Km" ], "Parameters": [ { "Name": "Start value", "Value": 37.8, "Unit": "µmol/l" }, { "Name": "MinValue", "Value": 1.0, "Unit": "µmol/l" }, { "Name": "MaxValue", "Value": 378.0, "Unit": "µmol/l" } ] }, { "Name": "kcat UGT1A4", "Scaling": "Linear", "LinkedParameters": [ "po 3 mg (solution)|Midazolam-UGT1A4-Optimized|kcat", "po 0.003 mg (solution)|Midazolam-UGT1A4-Optimized|kcat", "iv 1 mg (5 min)|Midazolam-UGT1A4-Optimized|kcat", "iv 0.001 mg (5 min)|Midazolam-UGT1A4-Optimized|kcat" ], "Parameters": [ { "Name": "Start value", "Value": 4.7586206897, "Unit": "1/min" }, { "Name": "MinValue", "Value": 0.0, "Unit": "1/min" }, { "Name": "MaxValue", "Value": 47.5862068966, "Unit": "1/min" } ] }, { "Name": "P (interstitial->intracellular)", "Scaling": "Log", "LinkedParameters": [ "po 3 mg (solution)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "po 0.003 mg (solution)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "iv 1 mg (5 min)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (interstitial->intracellular)", "iv 0.001 mg (5 min)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (interstitial->intracellular)", "po 3 mg (solution)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "po 3 mg (solution)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "po 0.003 mg (solution)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "iv 1 mg (5 min)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|Duodenum_int_Duodenum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|UpperIleum_int_UpperIleum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|LowerIleum_int_LowerIleum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|Caecum_int_Caecum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Midazolam|P (intracellular->interstitial)", "iv 0.001 mg (5 min)|Neighborhoods|Rectum_int_Rectum_cell|Midazolam|P (intracellular->interstitial)" ], "Parameters": [ { "Name": "Start value", "Value": 0.0651237007, "Unit": "cm/min" }, { "Name": "MinValue", "Value": 1E-05, "Unit": "cm/min" }, { "Name": "MaxValue", "Value": 0.1, "Unit": "cm/min" } ] }, { "Name": "Reference concentration", "Scaling": "Log", "LinkedParameters": [ "po 3 mg (solution)|GABRG2|Reference concentration", "po 0.003 mg (solution)|GABRG2|Reference concentration", "iv 1 mg (5 min)|GABRG2|Reference concentration", "iv 0.001 mg (5 min)|GABRG2|Reference concentration" ], "Parameters": [ { "Name": "Start value", "Value": 1.0, "Unit": "µmol/l" }, { "Name": "MinValue", "Value": 0.001, "Unit": "µmol/l" }, { "Name": "MaxValue", "Value": 100.0, "Unit": "µmol/l" } ] } ], "Analyses": [ { "Name": "Time Profile", "Type": "ParameterIdentificationTimeProfileChart", "Chart": { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "mg/l", "Dimension": "Concentration (mass)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" }, { "Unit": "%", "Dimension": "Fraction", "Type": "Y2", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Dash", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "yAxisType": "Y2", "VisibleInLegend": false, "Color": "#0000FF", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "yAxisType": "Y2", "VisibleInLegend": false, "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)-Midazolam-N-Glucuronide-Kidney-Urine-ArithmeticMean", "X": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)|Time", "Y": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticMean", "CurveOptions": { "yAxisType": "Y2", "VisibleInLegend": false, "Color": "#008000", "LegendIndex": 4, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)|Time", "Y": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "VisibleInLegend": false, "Color": "#FF00FF", "LegendIndex": 5, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)|Time", "Y": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "VisibleInLegend": false, "Color": "#FF8000", "LegendIndex": 6, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)-Midazolam-N-Glucuronide-Kidney-Urine-ArithmeticMean", "X": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|Time", "Y": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticMean", "CurveOptions": { "yAxisType": "Y2", "VisibleInLegend": false, "Color": "#00C0C0", "LegendIndex": 7, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "yAxisType": "Y2", "VisibleInLegend": false, "Color": "#C000C0", "LegendIndex": 8, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)-Midazolam-Kidney-Urine-ArithmeticMean", "X": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Y": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean", "CurveOptions": { "yAxisType": "Y2", "VisibleInLegend": false, "Color": "#C000C0", "LegendIndex": 9, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)|Time", "Y": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "VisibleInLegend": false, "Color": "#C04000", "LegendIndex": 10, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "Time Profile", "Settings": { "SideMarginsEnabled": true, "LegendPosition": "Bottom", "BackColor": "#FFFFFF", "DiagramBackColor": "#FFFFFF" } } } ] }, { "Name": "PI Tablet 7.5 mg", "Simulations": [ "po 7.5 mg (tablet)" ], "Configuration": { "LLOQMode": "SimulationOutputAsObservedDataLLOQ", "RemoveLLOQMode": "Never", "CalculateJacobian": false, "Algorithm": { "Name": "Monte - Carlo", "Properties": [ { "Name": "BreakCondition", "Value": 0.001 }, { "Name": "InitialAlpha", "Value": 30.0 }, { "Name": "MaxIterations", "Value": 10000.0 } ] } }, "OutputMappings": [ { "Scaling": "Log", "Path": "po 7.5 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)" }, { "Scaling": "Log", "Path": "po 7.5 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)" }, { "Scaling": "Log", "Path": "po 7.5 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)" }, { "Scaling": "Log", "Path": "po 7.5 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)" }, { "Scaling": "Log", "Path": "po 7.5 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)" }, { "Scaling": "Log", "Path": "po 7.5 mg (tablet)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)" } ], "IdentificationParameters": [ { "Name": "Dissolution time (50% dissolved)", "Scaling": "Linear", "LinkedParameters": [ "po 7.5 mg (tablet)|Applications|po 7.5 mg|Tablet (Dormicum)|Dissolution time (50% dissolved)" ], "Parameters": [ { "Name": "Start value", "Value": 10.0, "Unit": "min" }, { "Name": "MinValue", "Value": 0.01, "Unit": "min" }, { "Name": "MaxValue", "Value": 100.0, "Unit": "min" } ] }, { "Name": "Dissolution shape", "Scaling": "Linear", "LinkedParameters": [ "po 7.5 mg (tablet)|Applications|po 7.5 mg|Tablet (Dormicum)|Dissolution shape" ], "Parameters": [ { "Name": "Start value", "Value": 5.0 }, { "Name": "MinValue", "Value": 0.1 }, { "Name": "MaxValue", "Value": 10.0 } ] } ] }, { "Name": "PI Korean (Yu 2004 study)", "Simulations": [ "iv 1 mg (2 min)" ], "Configuration": { "LLOQMode": "SimulationOutputAsObservedDataLLOQ", "RemoveLLOQMode": "Never", "CalculateJacobian": false, "Algorithm": { "Name": "Levenberg - Marquardt (MPFit)", "Properties": [ { "Name": "ftol", "Value": 0.001 }, { "Name": "xtol", "Value": 1E-06 }, { "Name": "gtol", "Value": 1E-10 }, { "Name": "stepfactor", "Value": 100.0 }, { "Name": "maxiter", "Value": 200.0 }, { "Name": "maxfev", "Value": 0.0 }, { "Name": "epsfcn", "Value": 1E-09 } ] } }, "OutputMappings": [ { "Scaling": "Log", "Path": "iv 1 mg (2 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "ObservedData": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)" } ], "IdentificationParameters": [ { "Name": "Reference concentration", "Scaling": "Linear", "LinkedParameters": [ "iv 1 mg (2 min)|CYP3A4|Reference concentration" ], "Parameters": [ { "Name": "Start value", "Value": 4.32, "Unit": "µmol/l" }, { "Name": "MinValue", "Value": 0.0, "Unit": "µmol/l" }, { "Name": "MaxValue", "Value": 43.2, "Unit": "µmol/l" } ] } ], "Analyses": [ { "Name": "Time Profile", "Type": "ParameterIdentificationTimeProfileChart", "Chart": { "Axes": [ { "Unit": "h", "Dimension": "Time", "Type": "X", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "None", "Scaling": "Linear", "NumberMode": "Normal" }, { "Unit": "µmol/l", "Dimension": "Concentration (mass)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)-Midazolam-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)|Time", "Y": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean", "CurveOptions": { "VisibleInLegend": false, "Color": "#FF0000", "LegendIndex": 1, "LineStyle": "None", "Symbol": "Circle" } }, { "Name": "iv 1 mg (2 min)-Midazolam-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "iv 1 mg (2 min)|Organism|PeripheralVenousBlood|Midazolam|Plasma (Peripheral Venous Blood)", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 2 } } ], "Name": "Time Profile" } } ] } ], "ObservedData": [ { "Name": "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 104.0 }, { "Name": "Study Id", "Value": "Bornemann 1986" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/2936766" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "1 h after a meal" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 18.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 1.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fed" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01700745, 0.02676059, 0.0326278321, 0.035018, 0.03501306, 0.03600895, 0.02889098, 0.02488269, 0.01361774, 0.01025107, 0.006510167, 0.00500612054, 0.00291831815 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 1.5, 1.75, 2.0, 2.25, 2.5, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 11.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 365.0 }, { "Name": "Study Id", "Value": "Olkkola 1993" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8453848" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, 15 mg tablets, Hoffmann-La Roche Ltd." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00126658182, 0.0367308743, 0.0354642943, 0.0278648082, 0.022798501, 0.0151989851, 0.0113992356, 0.00633292133, 0.0050663217, 0.00379974535, 2.06476392E-10 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0003656307, 0.0274223015, 0.04424132, 0.0475319922, 0.0482632481, 0.0468007326, 0.0361974426, 0.02193784, 0.0142596, 0.008775137, 0.0007312614 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 18.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 51.0 }, { "Name": "Study Id", "Value": "Allonen 1981" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6117393" }, { "Name": "Source", "Value": "Fig. 3A" }, { "Name": "Grouping", "Value": "oral" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Unknown" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0248121656, 0.02821109, 0.0132558132, 0.0220930167, 0.027191421, 0.0193738714, 0.0112164533, 0.0135957031, 0.0176744238, 0.0139355967, 0.0142754912, 0.0186940953 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0103398925, 0.173148468, 0.173828289, 0.153774574, 0.1530948, 0.13066192, 0.120125219, 0.105169944, 0.08647584, 0.0616636835, 0.0307334531, 0.01509839 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.166666672, 0.333333343, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 7.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 52.0 }, { "Name": "Study Id", "Value": "Allonen 1981" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6117393" }, { "Name": "Source", "Value": "Fig. 3A" }, { "Name": "Grouping", "Value": "iv" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.075 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.007817535, 0.00781752, 0.0115563506, 0.0146153867, 0.007817535, 0.0183542017, 0.0112164626, 0.022093026, 0.02447227, 0.0251520574, 0.03908766, 0.0346690528, 0.0214132387 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.19422181, 0.178586766, 0.167030409, 0.158872962, 0.14391771, 0.138139531, 0.12080501, 0.1024508, 0.08069767, 0.05588551, 0.04194991, 0.0297137741, 0.0113595705 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0833333358, 0.166666672, 0.333333343, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 53.0 }, { "Name": "Study Id", "Value": "Backman 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8549036" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, tablet" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0100960769, 0.0240217019, 0.0146219041, 0.00939981, 0.00974792, 0.008355376, 0.005222097, 0.00348140835, "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00858715549, 0.04656881, 0.04348624, 0.0374311879, 0.023669729, 0.01706422, 0.01045872, 0.007486238, 0.00506422, 0.003302752 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 55.0 }, { "Name": "Study Id", "Value": "Backman 1998" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/9591931" }, { "Name": "Source", "Value": "Fig. 1 & Tab. 1" }, { "Name": "Grouping", "Value": "Phase I (Control (Perpetrator Placebo))" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 9.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum 7.5-mg tablet, Ho€mann-La Roche" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.03886638, 0.0388664119, 0.03765183, 0.0340080932, 0.0291497968, 0.0218623411, 0.0157894827, "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 2E-09 }, "Values": [ 0.0009999999, 0.0251012184, 0.0473684222, 0.05384615, 0.05425101, 0.04574899, 0.02712551, 0.01862348, 0.0145748993, 0.008906882, 0.006477733 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 112.0 }, { "Name": "Study Id", "Value": "Chung 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16580903" }, { "Name": "Source", "Value": "Fig. 2" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 18.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "0.075 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Syrup" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01244534, 0.005113894, 0.004263865, 0.00511541869, 0.00324032316, 0.00204784214, 0.00102354 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0223580711, 0.0184655786, 0.0145730795, 0.0110222707, 0.006135914, 0.003977728, 0.002044797 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 172.0 }, { "Name": "Study Id", "Value": "Gorski 1998" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/9728893" }, { "Name": "Source", "Value": "Fig. 2 & Tab. 1" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Whole Blood" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "4 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "stable isotope 15N3-midazolam" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01054974, 0.00625527976, 0.00694212364, 0.005121788, 0.00491813524, 0.003962862, 0.00232239813, 0.001847954, 0.00102569791, 0.001165137, 0.001145631 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01106758, 0.0125001809, 0.01106758, 0.008853939, 0.008501889, 0.007919147, 0.00584143866, 0.004487272, 0.00355353672, 0.002930626, 0.001875546 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 174.0 }, { "Name": "Study Id", "Value": "Gorski 1998" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/9728893" }, { "Name": "Source", "Value": "Fig. 2 & Tab. 1" }, { "Name": "Grouping", "Value": "iv Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Whole Blood" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.05 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01024524, 0.01590154, 0.015697401, 0.0195364784, 0.00921799, 0.007611912, 0.008236679, 0.007917028, 0.00766532635, 0.005223297, 0.002728171, 0.002520033, 0.001703482 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01640435, 0.03499131, 0.05034536, 0.03294821, 0.02361517, 0.01950017, 0.01594042, 0.0138442805, 0.0113171805, 0.00934902951, 0.006316024, 0.00431035925, 0.00300157187 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 176.0 }, { "Name": "Study Id", "Value": "Gorski 2003" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/12966371" }, { "Name": "Source", "Value": "Fig. 1, Tab 2 & 3" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 52.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Whole Blood" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "4 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.000625164656, 0.00526336068, 0.0055206297, 0.004509666, 0.00391413458, 0.003253146, 0.00285551813, 0.002936768, 0.002200273, 0.001837388, 0.001221479, 0.00101237, 0.0007693714 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.000919034763, 0.00626682537, 0.008664772, 0.008440037, 0.007907511, 0.008109928, 0.00711866, 0.005932589, 0.004817403, 0.00371172326, 0.00220343587, 0.001589032, 0.001131152 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 178.0 }, { "Name": "Study Id", "Value": "Gorski 2003" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/12966371" }, { "Name": "Source", "Value": "Fig. 1, Tab 2 & 3" }, { "Name": "Grouping", "Value": "iv Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 52.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Whole Blood" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.05 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.003681938, 0.012005399, 0.01431668, 0.008916349, 0.007024572, 0.01357058, 0.009450476, 0.007590396, 0.00529699, 0.005010053, 0.005476529, 0.002105015, 0.001690433 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.016341269, 0.03163564, 0.04292583, 0.02673086, 0.02257734, 0.0181321912, 0.01558304, 0.0125149693, 0.01112563, 0.008644944, 0.006288098, 0.00399441272, 0.00305699115 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - iv - f, 136kg, 36y (obese female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 180.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 7" }, { "Name": "Grouping", "Value": "iv - f, 136kg, 36y (obese female)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "parenteral midazolam preparation (5 mg/ml) was diluted to 50 ml with physiologic saline" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - iv - f, 136kg, 36y (obese female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0767379552, 0.0491974764, 0.03043449, 0.02037424, 0.02036083, 0.01421686, 0.01145977, 0.009168862, 0.007442451, 0.006437223, 0.004714279, 0.00449906, 0.00323704281, 0.00106657192 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - iv - f, 136kg, 36y (obese female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - iv - f, 61kg, 37y (normal female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 181.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 7" }, { "Name": "Grouping", "Value": "iv - f, 61kg, 37y (normal female)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "parenteral midazolam preparation (5 mg/ml) was diluted to 50 ml with physiologic saline" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - iv - f, 61kg, 37y (normal female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.06592891, 0.0546393022, 0.04206618, 0.03543239, 0.0303373113, 0.02065995, 0.015774589, 0.0144143207, 0.01006091, 0.008967583, 0.00462233229, 0.00358358887, 0.00168635091 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - iv - f, 61kg, 37y (normal female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - iv - m, 70kg, 32y (young male) - Midazolam - IV - 5 mg - Plasma - typical (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 182.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "iv - m, 70kg, 32y (young male)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "parenteral midazolam preparation (5 mg/ml) was diluted to 50 ml with physiologic saline" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - iv - m, 70kg, 32y (young male) - Midazolam - IV - 5 mg - Plasma - typical (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.09758067, 0.03907629, 0.05068097, 0.03636054, 0.0355256125, 0.0219095089, 0.01560594, 0.01297092, 0.007318588, 0.002545309, 0.00120531709 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - iv - m, 70kg, 32y (young male) - Midazolam - IV - 5 mg - Plasma - typical (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - iv - m, 80kg, 70y (elderly male) - Midazolam - IV - 5 mg - Plasma - typical (n=9)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 183.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "iv - m, 80kg, 70y (elderly male)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 9.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "parenteral midazolam preparation (5 mg/ml) was diluted to 50 ml with physiologic saline" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - iv - m, 80kg, 70y (elderly male) - Midazolam - IV - 5 mg - Plasma - typical (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.102461204, 0.0711742938, 0.0590841621, 0.0445235223, 0.0381829, 0.03146371, 0.02743706, 0.02298108, 0.02139012, 0.01428734, 0.01054188, 0.009149262, 0.005489816, 0.001157063 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - iv - m, 80kg, 70y (elderly male) - Midazolam - IV - 5 mg - Plasma - typical (n=9)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - po - f, 136kg, 36y (obese female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 184.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 7" }, { "Name": "Grouping", "Value": "po - f, 136kg, 36y (obese female)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - po - f, 136kg, 36y (obese female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.007423466, 0.0176505521, 0.02366277, 0.0153849395, 0.02181282, 0.01282684, 0.00691640936, 0.004515162, 0.005267244, 0.004714353, 0.003842969, 0.002790103, 0.001294081 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - po - f, 136kg, 36y (obese female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 0.75, 1.0, 1.5, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0, 15.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - po - f, 61kg, 37y (normal female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 185.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 7" }, { "Name": "Grouping", "Value": "po - f, 61kg, 37y (normal female)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - po - f, 61kg, 37y (normal female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.02494919, 0.06810079, 0.06073264, 0.03812619, 0.02354397, 0.027039431, 0.0173919, 0.0138326306, 0.00833227, 0.004156865, 0.00304370513, 0.00131994707 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - po - f, 61kg, 37y (normal female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - po - m, 70kg, 32y (young male) - Midazolam - PO - 10 mg - Plasma - typical (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 186.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "po - m, 70kg, 32y (young male)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - po - m, 70kg, 32y (young male) - Midazolam - PO - 10 mg - Plasma - typical (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.021964822, 0.09609839, 0.058166597, 0.04491255, 0.03249592, 0.03151618, 0.02300525, 0.0205675215, 0.01576695, 0.008134579, 0.003067903, 0.00151258893 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - po - m, 70kg, 32y (young male) - Midazolam - PO - 10 mg - Plasma - typical (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.17, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 1984 - po - m, 80kg, 70y (elderly male) - Midazolam - PO - 10 mg - Plasma - typical (n=9)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 187.0 }, { "Name": "Study Id", "Value": "Greenblat 1984" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6742481" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "po - m, 80kg, 70y (elderly male)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 9.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 1984 - po - m, 80kg, 70y (elderly male) - Midazolam - PO - 10 mg - Plasma - typical (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.04307222, 0.0908631161, 0.057741113, 0.04495055, 0.02881463, 0.0243284, 0.02263602, 0.0217814818, 0.0129127391, 0.01067114, 0.006724471, 0.001317428 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 1984 - po - m, 80kg, 70y (elderly male) - Midazolam - PO - 10 mg - Plasma - typical (n=9)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 188.0 }, { "Name": "Study Id", "Value": "Greenblat 2003" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/12891222" }, { "Name": "Source", "Value": "Fig. 2" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 25.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "6 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "oral solution" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.001701387, 0.00194444, 0.00121528015, 0.00115451007, 0.000911459036, 0.0009722223, 0.001032986, 0.0005468757, 0.0004253471, "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-09 }, "Values": [ 0.000499999966, 0.011059029, 0.01585938, 0.015494789, 0.01367188, 0.0117274309, 0.009600694, 0.006623264, 0.003585069, 0.002795139, 0.001762153 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Greenblat 2003 - with Perpetrator (GFJ) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 189.0 }, { "Name": "Study Id", "Value": "Greenblat 2003" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/12891223" }, { "Name": "Source", "Value": "Fig. 2" }, { "Name": "Grouping", "Value": "with Perpetrator (GFJ)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 25.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "6 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "oral solution" }, { "Name": "Food state", "Value": "Fed" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Greenblat 2003 - with Perpetrator (GFJ) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.002065975, 0.00267360918, 0.00230903085, 0.00182291993, 0.001701389, 0.001762152, 0.001276042, 0.0009722223, 0.000789930869, 0.000486111443 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Greenblat 2003 - with Perpetrator (GFJ) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-09 }, "Values": [ 0.000499999966, 0.01895833, 0.0260677114, 0.0247309, 0.0216319412, 0.01798611, 0.0156163191, 0.009965277, 0.0065625, 0.00498263864, 0.003098958 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Greenblat 2003 - with Perpetrator (GFJ) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 214.0 }, { "Name": "Study Id", "Value": "Gurley 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16432272" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Rifampicin (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 19.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.009608088, 0.01022137, 0.009539949, 0.00701865, 0.00572401658, 0.00490630371, 0.002589349, 0.001908006, 0.001839774, 0.00136286207 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 5.00000024E-05, 0.02200745, 0.02336745, 0.02459116, 0.02084052, 0.0172913615, 0.0139467092, 0.008279475, 0.005474252, 0.003895693, 0.002930243 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 216.0 }, { "Name": "Study Id", "Value": "Gurley 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16432272" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Clarithromycin (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 19.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.0155102, 0.0130612291, 0.006802723, 0.00761904428, 0.0062585, 0.00598640041, 0.005714289, 0.00380952423, "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 5.00000024E-05, 0.02068027, 0.02857143, 0.02394558, 0.02285714, 0.0179591812, 0.0152381007, 0.01006803, 0.007346939, 0.004353742, 0.003537415 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 218.0 }, { "Name": "Study Id", "Value": "Gurley 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16432272" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Black cohosh (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 19.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.0111564593, 0.01040816, 0.00802721, 0.007006798, 0.006054427, 0.004965987, 0.003537419, 0.002857143, 0.002653061, 0.00183673494 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 5.00000024E-05, 0.020136049, 0.02782313, 0.02510204, 0.01938775, 0.0181632712, 0.01537415, 0.01034014, 0.00727891224, 0.00489795953, 0.00380952423 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 219.0 }, { "Name": "Study Id", "Value": "Gurley 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16432272" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Milk thistle (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 19.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.009471895, 0.009063029, 0.008722315, 0.008926746, 0.004770021, 0.0044974396, 0.004020443, 0.00286201, 0.002521295, 0.00245315186 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 5.00000024E-05, 0.02739353, 0.0290971, 0.02487223, 0.021328792, 0.01662692, 0.01458262, 0.00967632048, 0.0066098813, 0.00463373074, 0.003884157 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 220.0 }, { "Name": "Study Id", "Value": "Gurley 2008a" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17495878" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Rifampicin (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01347522, 0.01595749, 0.0148936594, 0.01507067, 0.0154255806, 0.00921959151, 0.00514215, 0.00354611, 0.002304971, 0.002482276 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.028183952, 0.03739651, 0.03242463, 0.0260343086, 0.02548744, 0.0199763216, 0.01125846, 0.007860348, 0.00517116627, 0.00443263724 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 222.0 }, { "Name": "Study Id", "Value": "Gurley 2008a" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17495878" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Clarithromycin (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0401428, 0.0234458912, 0.01882777, 0.01456546, 0.0124334292, 0.007815294, 0.004973369, 0.00426347647, "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.05504765, 0.04686184, 0.0361899436, 0.0287152, 0.0247776117, 0.01870915, 0.0111897895, 0.008289148, 0.005743158, 0.00426289 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 224.0 }, { "Name": "Study Id", "Value": "Gurley 2008a" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17495878" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Goldenseal (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0203208514, 0.01782532, 0.014260239, 0.0121212192, 0.01212121, 0.009982179, 0.005704098, 0.004634581, 0.002317291, 0.002673796 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.04812834, 0.0420677438, 0.03565062, 0.0301247817, 0.02513369, 0.0208556186, 0.01212121, 0.009269162, 0.00570410024, 0.004991087 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 225.0 }, { "Name": "Study Id", "Value": "Gurley 2008a" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17495878" }, { "Name": "Source", "Value": "Methods" }, { "Name": "Grouping", "Value": "Control pre-Kava kava (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "8 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "8 mg, Bedford Laboratories" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0177619886, 0.01296625, 0.01154529, 0.0115453, 0.00746003864, 0.007992893, 0.00479573943, 0.00444049668, 0.002309059, 0.002841918 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.03534636, 0.03268206, 0.03197158, 0.02841918, 0.02575488, 0.02095915, 0.01385435, 0.008525755, 0.006039076, 0.00479573663 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 243.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "iv 0.15 mg/kg - Indiv. CH.B." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.15 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.304999977, 0.267, 0.254, 0.233, 0.177, 0.162, 0.124, 0.104, 0.053, 0.0470000021, 0.0339999981, 0.027, 0.013, 0.007, 0.005 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08333333, 0.166666672, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 244.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "iv 0.15 mg/kg - Indiv. K.M." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.15 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.298, 0.249000013, 0.235, 0.169, 0.144, 0.104, 0.0889999941, 0.054, 0.036, 0.027, 0.014, 0.012, 0.006, 0.006, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08333333, 0.166666672, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 245.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "iv 0.15 mg/kg - Indiv. E.Sch." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.15 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.424999982, 0.371999979, 0.32099998, 0.264, 0.206, 0.186999992, 0.142, 0.115, 0.063, 0.048, 0.0339999981, 0.029000001, 0.0159999989, 0.015, 0.011 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08333333, 0.166666672, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 246.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "iv 0.15 mg/kg - Indiv. R.H." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.15 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.290999979, 0.24, 0.226, 0.172, 0.142, 0.119, 0.0830000043, 0.055, 0.035, 0.024, 0.0159999989, 0.009, 0.00399999972, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08333333, 0.166666672, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 247.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "iv 0.15 mg/kg - Indiv. A.St." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.15 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.314, 0.233, 0.183, 0.183, 0.138000011, 0.107, 0.0690000057, 0.056, 0.037, 0.023, 0.018, 0.014, 0.007999999, 0.005, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08333333, 0.166666672, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 248.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "iv 0.15 mg/kg - Indiv. O.A." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.15 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.31, 0.281000018, 0.262, 0.22, 0.19, 0.171, 0.138000011, 0.121, 0.073, 0.053, 0.039, 0.03, 0.019, 0.01, 0.007 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08333333, 0.166666672, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 249.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 10 mg - Indiv. K.M." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.157, 0.078, 0.051, 0.038, 0.026, 0.021, 0.0159999989, 0.01, 0.006, 0.00199999986, 0.00199999986, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 250.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 10 mg - Indiv. O.A." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.17, 0.14, 0.100999996, 0.075, 0.055, 0.043, 0.024, 0.015, 0.012, 0.007999999, 0.00399999972, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 251.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 10 mg - Indiv. R.H." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.052, 0.082, 0.059, 0.045, 0.036, 0.023, 0.0159999989, 0.011, 0.006, 0.00399999972, 0.00199999986, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 252.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 20 mg - Indiv. A.St." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "20 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.142, 0.075, 0.053, 0.045, 0.026, 0.019, 0.013, 0.007999999, 0.006, 0.005, 0.00199999986, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 253.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 20 mg - Indiv. CH.B." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "20 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.336999983, 0.19, 0.13499999, 0.109, 0.081, 0.078, 0.05, 0.04, 0.025, 0.018, 0.009, 0.006, 0.00399999972 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 254.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 20 mg - Indiv. E.Sch." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "20 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.367, 0.28, 0.197000012, 0.177, 0.129, 0.102, 0.067, 0.049, 0.029000001, 0.025, 0.014, 0.011, 0.013 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 255.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 20 mg - Indiv. K.M." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "20 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.08, 0.126, 0.077, 0.073, 0.057, 0.049, 0.0319999978, 0.025, 0.011, 0.007999999, 0.00399999972, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 256.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 20 mg - Indiv. O.A." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "20 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.162, 0.139, 0.11, 0.099, 0.079, 0.075, 0.059, 0.046, 0.036, 0.026, 0.014, 0.007999999, 0.00399999972 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 257.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 20 mg - Indiv. R.H." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "20 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.121, 0.223, 0.133, 0.1, 0.076, 0.0639999956, 0.052, 0.028, 0.0169999991, 0.011, 0.0045, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 258.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 40 mg - Indiv. A.St." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "40 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 4E-09 }, "Values": [ 0.368, 0.163, 0.104, 0.098, 0.057, 0.042, 0.025, 0.0159999989, 0.009, 0.007, 0.00399999972, 0.00199999986, 0.00199999986 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 259.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 40 mg - Indiv. CH.B." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "40 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.953, 0.45, 0.285, 0.259, 0.209, 0.165, 0.105, 0.087, 0.042, 0.0339999981, 0.019, 0.01, 0.01 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv.", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 260.0 }, { "Name": "Study Id", "Value": "Heizmann 1983" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/6138080" }, { "Name": "Source", "Value": "Tab. 1" }, { "Name": "Grouping", "Value": "po 40 mg - Indiv. E.Sch." }, { "Name": "Data type", "Value": "individual" }, { "Name": "N", "Value": 1.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "40 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv.|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 1.449, 0.538, 0.39, 0.315, 0.264, 0.207, 0.126, 0.109, 0.086, 0.0690000057, 0.0470000021, 0.036, 0.027 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv.|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 261.0 }, { "Name": "Study Id", "Value": "Hohmann 2015" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/25588320" }, { "Name": "Source", "Value": "Fig.1, Table 1 & 3" }, { "Name": "Grouping", "Value": "iv 0.001 mg" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.001 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 4.187355E-05, 1.92918087E-05, 1.438149E-05, 1.10110705E-05, 9.13471649E-06, 6.811425E-06, 5.079031E-06, 3.889972E-06, 3.31537512E-06, 2.222763E-06, 1.11182E-06, 8.085315E-07, 5.008498E-07, 1.050899E-07 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 262.0 }, { "Name": "Study Id", "Value": "Hohmann 2015" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/25588320" }, { "Name": "Source", "Value": "Fig.1, Table 1 & 3" }, { "Name": "Grouping", "Value": "iv 1 mg" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.041397173, 0.0171383619, 0.0134773208, 0.01004696, 0.008792599, 0.0067339344, 0.004888967, 0.003949772, 0.00336645, 0.0023181478, 0.001223207, 0.000866071437, 0.000551027129, 6.59545549E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 263.0 }, { "Name": "Study Id", "Value": "Hohmann 2015" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/25588320" }, { "Name": "Source", "Value": "Fig.1, Table 1 & 3" }, { "Name": "Grouping", "Value": "po 0.003 mg" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "0.003 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Oral solution" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 5.069215E-06, 1.01596206E-05, 9.379759E-06, 7.781137E-06, 5.355181E-06, 3.785173E-06, 3.31355818E-06, 2.537735E-06, 1.794832E-06, 9.47040633E-07, 5.8665006E-07, 3.732608E-07, 9.69917764E-08 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 264.0 }, { "Name": "Study Id", "Value": "Hohmann 2015" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/25588320" }, { "Name": "Source", "Value": "Fig.1, Table 1 & 3" }, { "Name": "Grouping", "Value": "po 3 mg" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "3 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Oral solution" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.005147309, 0.008555996, 0.007098001, 0.006912567, 0.00501849828, 0.00384361041, 0.002943682, 0.002378262, 0.00168199, 0.000776520639, 0.0005352838, 0.0003998114, 5.048453E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 267.0 }, { "Name": "Study Id", "Value": "Hyland 2009" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/19371318" }, { "Name": "Source", "Value": "Tab. 3" }, { "Name": "Grouping", "Value": "3-mg oral dose (as fraction of dose)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam-N-Glucuronide" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Kidney" }, { "Name": "Compartment", "Value": "Urine" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "3 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 502.899 }, "Values": [ 0.009870377 ], "Dimension": "Fraction" } ], "QuantityInfo": { "Name": "Avg", "Path": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 502.899 }, "Values": [ 0.0128513183 ], "Dimension": "Fraction" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 268.0 }, { "Name": "Study Id", "Value": "Hyland 2009" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/19371318" }, { "Name": "Source", "Value": "Tab. 3" }, { "Name": "Grouping", "Value": "1-mg i.v. dose (as fraction of dose)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam-N-Glucuronide" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Kidney" }, { "Name": "Compartment", "Value": "Urine" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 502.899 }, "Values": [ 0.01007361 ], "Dimension": "Fraction" } ], "QuantityInfo": { "Name": "Avg", "Path": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|ObservedData|Kidney|Urine|Midazolam-N-Glucuronide|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 502.899 }, "Values": [ 0.0216467883 ], "Dimension": "Fraction" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 275.0 }, { "Name": "Study Id", "Value": "Kharasch 1997" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/9232132" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "typical representative" }, { "Name": "N", "Value": 9.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Individual" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.02807617, 0.02201741, 0.01424062, 0.007675129, 0.006201037, 0.004860217, 0.003732899, 0.00253738579, 0.00188920787, 0.001572301, 0.001256607 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 1.2166667, 2.1833334, 3.1833334, 4.16666651, 5.1833334, 7.16666651, 9.183333, 11.166667, 13.166667 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 279.0 }, { "Name": "Study Id", "Value": "Kharasch 2004" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/15536460" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "iv Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0226, 0.0158999991, 0.00945, 0.00675, 0.00413, 0.00373999984, 0.0033, 0.00271, 0.00232, 0.00161, 0.00131, 0.00112, 0.00081, 0.0007, 0.00051 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0833333358, 0.25, 0.5, 1.0, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 285.0 }, { "Name": "Study Id", "Value": "Kharasch 2004" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/15536460" }, { "Name": "Source", "Value": "Fig. 4" }, { "Name": "Grouping", "Value": "po #1 Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "3 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Solution" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00205999985, 0.00405, 0.00366000016, 0.00116, 0.00217000023, 0.00105, 0.00097, 0.00089, 0.00067, 0.00078, 0.00059, 0.00038, 0.00039, 0.00027, 0.00031, 0.00028 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00199999986, 0.00506, 0.00744000031, 0.00617, 0.00575, 0.00439, 0.00397, 0.00358, 0.00269, 0.0025, 0.00169000006, 0.00131, 0.00111, 0.00092, 0.00069, 0.00061 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0833333358, 0.25, 0.5, 1.0, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 303.0 }, { "Name": "Study Id", "Value": "Kharasch 2011" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/21562488" }, { "Name": "Source", "Value": "Fig. 2A" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "3 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 3.86847023E-05, 3.868484E-05, 0.004177949, 0.00599613274, 0.004874278, 0.005415863, 0.002901354, 0.00270793, 0.002398453, 0.002359767, 0.002359768, 0.00189555192, 0.001624758, 0.00170212809, 0.001199226, 0.001276596, 0.000967118249, 0.00069632486, 0.0006576406, 0.0005029012, 0.000425531878 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.000232108287, 0.003288201, 0.007388782, 0.01148936, 0.0140425507, 0.0126499, 0.008433268, 0.0080851065, 0.0075435196, 0.007079304, 0.006576402, 0.005725338, 0.00495164376, 0.00398452627, 0.003365571, 0.003172147, 0.002591876, 0.00193423615, 0.001470019, 0.001276596, 0.000889748568 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.17, 0.25, 0.33, 0.5, 0.75, 1.0, 1.17, 1.25, 1.33, 1.5, 1.75, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 9.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 293.0 }, { "Name": "Study Id", "Value": "Kharasch 2011" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/21562488" }, { "Name": "Source", "Value": "Fig. 1A" }, { "Name": "Grouping", "Value": "iv Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.02874158, 0.00661397446, 0.003490145, 0.002461803, 0.00194341387, 0.001855472, 0.001549582, 0.001349989, 0.00113199791, 0.0008010316, 0.000900100742, 0.0006736665, 0.00089060684, 0.0005934198, 0.00047508048, 0.0005961453, 0.000407580927, 0.00052333757, 0.0004446983, 0.0004364775 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.061621327, 0.02618743, 0.02044153, 0.01441864, 0.01138242, 0.009399509, 0.007849926, 0.00733712129, 0.006630036, 0.0055370233, 0.004892001, 0.004273728, 0.003733594, 0.003225206, 0.00240667886, 0.00192140392, 0.001450004, 0.001355281, 0.00110664894, 0.0009036291 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.08, 0.17, 0.33, 0.5, 0.75, 1.0, 1.17, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 341.0 }, { "Name": "Study Id", "Value": "Link 2008" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/18537963" }, { "Name": "Source", "Value": "Fig. 1, Tab.1" }, { "Name": "Grouping", "Value": "iv Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 8.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0880812258, 0.0125105111, 0.006980721, 0.00457891729, 0.00287832483, 0.003610662, 0.002920249, 0.00191814406, 0.001333541, 0.0007206521, 0.000587888, 0.000418629177, 3.448249E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.1773568, 0.04757944, 0.03316938, 0.02859046, 0.02571214, 0.019512929, 0.01578181, 0.0119768111, 0.006336411, 0.00342422375, 0.001850466, 0.00131769711, 8.528557E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0833333358, 0.166666672, 0.333333343, 0.5, 0.6666667, 1.0, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 343.0 }, { "Name": "Study Id", "Value": "Link 2008" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/18537963" }, { "Name": "Source", "Value": "Fig. 5, Tab.3" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 8.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "7.5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum® Hoffmann-LaRoche Ltd" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01752388, 0.0226843618, 0.0212757215, 0.01674503, 0.009470755, 0.007813723, 0.00691792648, 0.003469483, 0.002202336, 0.001160009, 0.000896239944, 0.0006403636, 9.3616145E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01205609, 0.0483564921, 0.04535368, 0.03822668, 0.0271565616, 0.02240516, 0.01697065, 0.0108343493, 0.00753407925, 0.003968331, 0.002045996, 0.001278582, 0.0001142891 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.166666672, 0.333333343, 0.5, 0.6666667, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 351.0 }, { "Name": "Study Id", "Value": "Majumdar 2007" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17463213" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.06252381, 0.006606312, 0.004868875, 0.00294502964, 0.004042586, 0.00164468307, 0.00162751426, 0.00137018657, 0.000418113254, 0.000571823446, 0.0006887002, 0.000504494761, 0.0003165938, 0.0001559038 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0598561, 0.0353340022, 0.026041301, 0.02085821, 0.01741662, 0.011648369, 0.008704804, 0.005903157, 0.00429072, 0.002463578, 0.00169400894, 0.000882639142, 0.0004350651, 0.000119760392 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.03, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Majumdar 2007 - po with Perpetrator (Aprepitant) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 352.0 }, { "Name": "Study Id", "Value": "Majumdar 2007" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17463213" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "po with Perpetrator (Aprepitant)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 1.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Majumdar 2007 - po with Perpetrator (Aprepitant) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.130616412, 0.00727993436, 0.00684816856, 0.006628579, 0.005458621, 0.002111112, 0.00166764343, 0.00167329924, 0.00130358548, 0.00143378659, 0.0012504278, 0.0009808078, 0.0007424678, 0.000437516021 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Majumdar 2007 - po with Perpetrator (Aprepitant) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0959241, 0.03683537, 0.02752701, 0.02204822, 0.0181566682, 0.0149519788, 0.0113296611, 0.008466635, 0.006595946, 0.00447303569, 0.00343672279, 0.00200080476, 0.001214332, 0.0004997988 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Majumdar 2007 - po with Perpetrator (Aprepitant) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 1.03, 1.25, 1.5, 1.75, 2.0, 2.5, 3.0, 4.0, 5.0, 7.0, 9.0, 13.0, 17.0, 25.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 367.0 }, { "Name": "Study Id", "Value": "Olkkola 1993" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8453848" }, { "Name": "Source", "Value": "Fig. 3" }, { "Name": "Grouping", "Value": "iv Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.05 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, 1 mg/ml injection, Hoffmann-La Roche Ltd." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0171723869, 0.0117503349, 0.00903871749, 0.00813366, 0.008134861, 0.003615496, 0.001806546, 0.00180894032, 0.00090267614, 0.00180655, 0.000903872 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.06383096, 0.0520174429, 0.03762138, 0.03244995, 0.02432209, 0.0173012409, 0.01174518, 0.007297114, 0.005041598, 0.003176075, 0.00278657 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 7.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 369.0 }, { "Name": "Study Id", "Value": "Olkkola 1994" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8181191" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 9.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "7.5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, Hoffmann-La Roche" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.0095682, "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.004093904, 0.0183202587, 0.01903854, 0.01712886, 0.0103091, 0.006675958, 0.003608443, 0.002604661, 0.001976102, 0.000183417011 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 17.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 388.0 }, { "Name": "Study Id", "Value": "Phimmasone 2001" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/11753266" }, { "Name": "Source", "Value": "Fig. 1, Tab.1&2" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "bolus" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0326392762, 0.01466147, 0.00405513169, 0.00665137731, 0.004753922, 0.00341860787, 0.00337769184, 0.003866261, 0.003685795, 0.003240941, 0.00358224381, 0.00290049776, 0.002275486, 0.001601458, 0.001909692, 0.00138455292, 0.000564341433, 0.0006479579, 0.0006103216 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.088439934, 0.04364608, 0.0241063181, 0.0211012177, 0.01415264, 0.009784649, 0.009488017, 0.009106511, 0.008563273, 0.007970452, 0.00780733628, 0.006831773, 0.006165917, 0.004970392, 0.004767931, 0.002913667, 0.002075948, 0.00189086189, 0.00141797191 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0333333351, 0.0833333358, 0.166666672, 0.25, 0.5, 1.0, 1.08333337, 1.16666663, 1.25, 1.33333337, 1.5, 1.83333337, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Reitman 2011 - Week 4 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 395.0 }, { "Name": "Study Id", "Value": "Reitman 2011" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/21191377" }, { "Name": "Source", "Value": "Fig. 1a" }, { "Name": "Grouping", "Value": "Week 4 after Perpetrator (Rifampicin)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 11.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 1320.0 }, { "Name": "Formulation", "Value": "Syrup" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Reitman 2011 - Week 4 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.008415867, 0.0045, 0.00181730778, 0.000865384645, 0.0005192308, 0.00023798077 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Reitman 2011 - Week 4 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 1321.0, 1322.0, 1324.0, 1326.0, 1328.0, 1332.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 400.0 }, { "Name": "Study Id", "Value": "Saari 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16580904" }, { "Name": "Source", "Value": "Fig. 3" }, { "Name": "Grouping", "Value": "po Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "7.5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, 7.5-mg tablet; Roche" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.01333333, 0.009599999, 0.005866663, 0.004000002, 0.00453333, 0.005066669, "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 2E-09 }, "Values": [ 0.0009999999, 0.009866667, 0.0192, 0.01866667, 0.0165333319, 0.0130666709, 0.0101333307, 0.004533333, 0.00213333312 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 403.0 }, { "Name": "Study Id", "Value": "Saari 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16580904" }, { "Name": "Source", "Value": "Fig. 2" }, { "Name": "Grouping", "Value": "iv Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.05 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, 1-mg/mL injection; Roche" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.0128571391, 0.008303574, 0.005892855, 0.004017851, 0.004285713, "NaN", "NaN", "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 2E-09 }, "Values": [ 0.0009999999, 0.05919643, 0.04901786, 0.03642857, 0.0275892783, 0.0214285683, 0.0155357094, 0.01125, 0.00669642864, 0.003482143, 0.001339286 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 414.0 }, { "Name": "Study Id", "Value": "Schwagmeier 1998" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/9764959" }, { "Name": "Source", "Value": "Fig. 2" }, { "Name": "Grouping", "Value": "iv administration" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 8.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.02716936, 0.02747169, 0.0223392285, 0.01750905, 0.01781162, 0.01811282, 0.01509431, 0.0126799094, 0.01690527, 0.006037373, 0.0072452696, 0.006943384, 0.004528637, "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.116827205, 0.1041465, 0.102031596, 0.0896514952, 0.08693279, 0.07998593, 0.07514915, 0.06185713, 0.0539987125, 0.04160297, 0.0331307, 0.0249426011, 0.01343272, 0.00422605826 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.05, 0.1, 0.15, 0.2, 0.25, 0.333333343, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 415.0 }, { "Name": "Study Id", "Value": "Smith 1981" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6116606" }, { "Name": "Source", "Value": "Fig. 3" }, { "Name": "Grouping", "Value": "iv 5 mg" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.102065131, 0.09058138, 0.08197502, 0.07337115, 0.06477959, 0.0590676144, 0.0512194745, 0.0391042, 0.0327280052, 0.0192670915, 0.0126505895, 0.00618778029, 0.00439612474 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.16, 0.25, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 416.0 }, { "Name": "Study Id", "Value": "Smith 1981" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6116606" }, { "Name": "Source", "Value": "Fig. 4" }, { "Name": "Grouping", "Value": "oral solution 10 mg" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Solution" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00140416308, 0.01885978, 0.0418989845, 0.0611005723, 0.05135668, 0.0461532138, 0.04200329, 0.0319677778, 0.02575769, 0.0171646271, 0.012082871, 0.005715175, 0.003191968 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.16, 0.25, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 417.0 }, { "Name": "Study Id", "Value": "Smith 1981" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/6116606" }, { "Name": "Source", "Value": "Fig. 5" }, { "Name": "Grouping", "Value": "oral tablet 10 mg" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Tablet" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00662233355, 0.033620134, 0.03712994, 0.0413257666, 0.0434608348, 0.0494660176, 0.03194598, 0.0232520122, 0.0137434211, 0.006558781, 0.0032040982 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 421.0 }, { "Name": "Study Id", "Value": "Szalat 2007" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17553741" }, { "Name": "Source", "Value": "Fig. 2" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 3.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.05 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "bolus, 1% midazolam (Rafa Ltd., Israel)" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0354878381, 0.0189124513, 0.0102648316, 0.007822184, 0.005941331, 0.00305279158, 0.00493148668, 0.003595687 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.06826481, 0.06508359, 0.03850279, 0.02691856, 0.0163092986, 0.0155492593, 0.01, 0.008666103 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0833333358, 0.25, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 423.0 }, { "Name": "Study Id", "Value": "Templeton 2010" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/20739919" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "oral solution" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 0.001 }, "Values": [ 0.0005, 0.01991837, 0.01697959, 0.01077551, 0.00636734674, 0.004081633, 0.002612245, 0.00130612194, 0.0011428569, 0.0001632653 ], "Dimension": "Concentration (molar)", "Unit": "µmol/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.5, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 20.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 427.0 }, { "Name": "Study Id", "Value": "Tham 2006" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/16628140" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 28.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0362620763, 0.0338971578, 0.0370503925, 0.0362620652, 0.03626208, 0.03310884, 0.03626207 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0581005551, 0.03992551, 0.02592179, 0.0239851, 0.02026071, 0.009832402, 0.00670391 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 1.0, 1.5, 2.0, 3.5, 5.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 429.0 }, { "Name": "Study Id", "Value": "Thummel 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8646820" }, { "Name": "Source", "Value": "Tab. II" }, { "Name": "Grouping", "Value": "iv - female" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Kidney" }, { "Name": "Compartment", "Value": "Urine" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00059999997 ], "Dimension": "Fraction" } ], "QuantityInfo": { "Name": "Avg", "Path": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0027 ], "Dimension": "Fraction" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 430.0 }, { "Name": "Study Id", "Value": "Thummel 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8646820" }, { "Name": "Source", "Value": "Tab. II" }, { "Name": "Grouping", "Value": "iv - male" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Kidney" }, { "Name": "Compartment", "Value": "Urine" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.000900000043 ], "Dimension": "Fraction" } ], "QuantityInfo": { "Name": "Avg", "Path": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0028 ], "Dimension": "Fraction" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 431.0 }, { "Name": "Study Id", "Value": "Thummel 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8646820" }, { "Name": "Source", "Value": "Tab. II" }, { "Name": "Grouping", "Value": "po - female" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Kidney" }, { "Name": "Compartment", "Value": "Urine" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0008 ], "Dimension": "Fraction" } ], "QuantityInfo": { "Name": "Avg", "Path": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0031 ], "Dimension": "Fraction" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 432.0 }, { "Name": "Study Id", "Value": "Thummel 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8646820" }, { "Name": "Source", "Value": "Tab. II" }, { "Name": "Grouping", "Value": "po - male" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Kidney" }, { "Name": "Compartment", "Value": "Urine" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0017 ], "Dimension": "Fraction" } ], "QuantityInfo": { "Name": "Avg", "Path": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)|ObservedData|Kidney|Urine|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0047 ], "Dimension": "Fraction" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 468.0 }, { "Name": "Study Id", "Value": "Yeates 1996" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/8880291" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum tablet" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.12915121, 0.09421921, 0.0558576025, 0.066279605, "NaN", "NaN", "NaN", "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0689598, 0.0579323024, 0.0376251, 0.0260418989, 0.0162026, 0.0115996, 0.0090313, 0.00505984, 0.00263218, 0.000304767978 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 470.0 }, { "Name": "Study Id", "Value": "Zimmermann 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8720318" }, { "Name": "Source", "Value": "Fig. 3" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.06024532, 0.0471182577, 0.0293443035, 0.0182912368, 0.0151264137, 0.0122538013, 0.009375188, 0.00421438925, 0.00177203165 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 376.0 }, { "Name": "Study Id", "Value": "Olkkola 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8623953" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "day 6 (po) Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "7.5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.020975152, 0.0139834322, "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01924999, 0.0333624, 0.02637337, 0.01920152, 0.01201307, 0.00794386, 0.00497622928, 0.004393238, 0.00381091121, 0.000184149 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 17.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 375.0 }, { "Name": "Study Id", "Value": "Olkkola 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8623953" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "day 4 (iv) Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.05 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0541352332, 0.04252526, 0.02869672, 0.020577088, 0.01595714, 0.0107687106, 0.008157839, 0.005731124, 0.00496183475, 0.00456153043 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 374.0 }, { "Name": "Study Id", "Value": "Olkkola 1996" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8623953" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "day 1 (po) Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "7.5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01282656, "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01757065, 0.02588229, 0.02197114, 0.01694891, 0.01172271, 0.008344739, 0.00496766, 0.00418221, 0.003400338 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 49.0 }, { "Name": "Study Id", "Value": "Ahonen 1995" }, { "Name": "Reference", "Value": "http://www.ncbi.nlm.nih.gov/pubmed/8527290" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "7.5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, Hoffman-La-Roche, Switzerland" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.02309185, 0.0160241257, 0.0108415578, "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01563506, 0.02800338, 0.02350127, 0.01845495, 0.01176411, 0.008475058, 0.005322059, 0.004073787, 0.003505774, 0.0005447035 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 17.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 131.0 }, { "Name": "Study Id", "Value": "Eap 2004" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/15114429" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "7.5 mg Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 13.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "7.5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "GeometricStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 1.53742, 1.367254, 1.332074, 1.459321, 1.598724, 1.619698, 1.869382, 1.893907 ], "Dimension": "Dimensionless" } ], "QuantityInfo": { "Name": "Avg", "Path": "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.02333053, 0.01598724, 0.0138519, 0.0109552611, 0.007507092, 0.004882916, 0.002415566, 0.001491368 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 128.0 }, { "Name": "Study Id", "Value": "Eap 2004" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/15114429" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "0.075 mg Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 21.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "0.075 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "GeometricStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 1.598724, 1.332074, 1.497862, 1.557589, 1.821283, 1.728765, 1.640946 ], "Dimension": "Dimensionless" } ], "QuantityInfo": { "Name": "Avg", "Path": "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.000243664617, 0.0002282919, 0.00016056851, 0.000105810395, 6.53272436E-05, 5.09972961E-05, 3.82841426E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 419.0 }, { "Name": "Study Id", "Value": "Swart 2002" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/11851636" }, { "Name": "Source", "Value": "Fig. 2" }, { "Name": "Grouping", "Value": "day 5 Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 8.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.075 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum 3 mg/ml, Roche, Mijdrecht, the Netherlands" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.1171004, 0.02788104, 0.0245353188, 0.01784383, 0.01003719, 0.008921936, 0.0122676594, 0.008921932, 0.0089219315 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.428252816, 0.2063197, 0.1605948, 0.1215613, 0.101486996, 0.09033457, 0.07360595, 0.041263938, 0.02230483 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.17, 0.25, 0.33, 0.42, 0.5, 1.0, 2.0, 4.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 105.0 }, { "Name": "Study Id", "Value": "Bornemann 1986" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/2936766" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "1 h before a meal" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 18.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.01210635, 0.06488906, 0.06044231, 0.0583310723, 0.05318992, 0.04583131, 0.03500319, 0.02303062, 0.01697242, 0.0108552305, 0.00772142271, 0.00589542836, 0.004406638, 0.002738073 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 107.0 }, { "Name": "Study Id", "Value": "Bornemann 1986" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/2936766" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "fasting condition" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 18.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0113584995, 0.05099948, 0.05396478, 0.05207867, 0.0492015332, 0.0426961221, 0.0411976, 0.0307935122, 0.02144283, 0.01420879, 0.009087861, 0.007501276, 0.00466361549, 0.00260556513 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 106.0 }, { "Name": "Study Id", "Value": "Bornemann 1986" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/2936766" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "with a meal" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 18.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fed" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00721761165, 0.04272161, 0.0468351729, 0.0427081734, 0.0471543521, 0.04150267, 0.03920428, 0.02972177, 0.02285464, 0.01503755, 0.00968621, 0.006697373, 0.005077395, 0.00298104179, 0.00197421014 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 119.0 }, { "Name": "Study Id", "Value": "Darwish 2008" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/18076219" }, { "Name": "Source", "Value": "Fig. 4" }, { "Name": "Grouping", "Value": "iv" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 24.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.0079892315, 0.008363749, 0.00677951146, 0.00422048848, 0.00453239353, 0.00347843464, 0.0027484016, 0.00232843263, 0.0004485921, 0.0009798415, 0.0007348729, 0.000661305443, 0.0005211505, 0.000172057145 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-09 }, "Values": [ 0.000499999966, 0.03825684, 0.02978061, 0.0241723713, 0.0201737, 0.01614934, 0.01240241, 0.009792784, 0.008290795, 0.00654654671, 0.00469202641, 0.002620178, 0.001548889, 0.0009029115, 0.000212143088 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 9.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 118.0 }, { "Name": "Study Id", "Value": "Darwish 2008" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/18076219" }, { "Name": "Source", "Value": "Fig. 4" }, { "Name": "Grouping", "Value": "oral" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 24.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "Arith. SEM converted to arith. SD" } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.004195047, 0.007771452, 0.009980979, 0.00633512, 0.00590895768, 0.00486222, 0.00368016819, 0.00302823982, 0.00245733629, 0.0008855273, 0.000889059447, 0.000502281066, 0.0004533473, 0.000200476323 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-09 }, "Values": [ 0.000499999966, 0.00368580385, 0.0134596005, 0.0152569516, 0.01483785, 0.01383978, 0.01138811, 0.008619536, 0.007092616, 0.00575546827, 0.004236587, 0.002082325, 0.00117642607, 0.0006929882, 0.0001436343 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 0.17, 0.33, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 9.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1088.0 }, { "Name": "Study Id", "Value": "Lam 2003" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/14551182" }, { "Name": "Source", "Value": "Fig.1; Table I+II" }, { "Name": "Grouping", "Value": "Midazolam before Fluvoxamine" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "midazolam oral solution" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.06319037, 0.0637651458, 0.0360710174, 0.029060049, 0.02223811, 0.007474914, 0.00223767571, 0.001516093 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1086.0 }, { "Name": "Study Id", "Value": "Lam 2003" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/14551182" }, { "Name": "Source", "Value": "Fig.1; Table I+II" }, { "Name": "Grouping", "Value": "Midazolam before Ketoconazole" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 10.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "midazolam oral solution" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0538356043, 0.0338256, 0.0286835581, 0.02149377, 0.009658476, 0.005472284 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 4.0, 8.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "van Dyk 2018 - Midazolam in South Asian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=11)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 2001.0 }, { "Name": "Study Id", "Value": "van Dyk 2018" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/29572563" }, { "Name": "Source", "Value": "Fig. 1; Table 2" }, { "Name": "Grouping", "Value": "Midazolam in South Asian at baseline" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 11.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Pfizer midazolam for injection (Pfizer, NSW, Australia)" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "van Dyk 2018 - Midazolam in South Asian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0001397206, 0.000379241916, 0.000658682839, 0.000618763035, 0.000299401319, 0.000279441621, 0.000359281228, 0.000259481021 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "van Dyk 2018 - Midazolam in South Asian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 2E-10 }, "Values": [ 0.001257485, 0.003333333, 0.00554890232, 0.005429142, 0.00251497, 0.001616766, 0.00117764494, 0.0008183632 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "van Dyk 2018 - Midazolam in South Asian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 2.0, 3.0, 4.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 2000.0 }, { "Name": "Study Id", "Value": "van Dyk 2018" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/29572563" }, { "Name": "Source", "Value": "Fig. 1; Table 2" }, { "Name": "Grouping", "Value": "Midazolam in Caucasian at baseline" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 19.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Pfizer midazolam for injection (Pfizer, NSW, Australia)" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0001996003, 0.000499002, 0.000838323554, 0.000838322565, 0.000399201235, 0.0003592818, 0.0001996011, 0.0002794408 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 2E-10 }, "Values": [ 0.00109780394, 0.00502994, 0.007185629, 0.006886228, 0.003433134, 0.002335329, 0.001796407, 0.00139720587 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 2.0, 3.0, 4.0, 6.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 353.0 }, { "Name": "Study Id", "Value": "Markert 2013" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/23748747" }, { "Name": "Source", "Value": "personal (Haefeli)" }, { "Name": "Grouping", "Value": "Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 11.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "3 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum 5mg/5ml Solution" }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00170265161, 0.00141185545, 0.00117907755, 0.0009026386 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00507270172, 0.00407387363, 0.00336817279, 0.002392267 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 2.0, 2.5, 3.0, 4.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1096.0 }, { "Name": "Study Id", "Value": "Prueksaritanont 2017" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/27943276" }, { "Name": "Source", "Value": "Fig. 1a; Table 1" }, { "Name": "Grouping", "Value": "Midazolam in microdosecocktail alone" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "10 µg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "microdose cocktail containing 10 µg midazolam (Solution A: diluting 2 mg/mL midazolam syrup (Ranbaxy Pharmaceuticals) with water to 10 µg/mL midazolam solution), 375 µg DABE, 10 µg of pitavastatin, 50 µg rosuvastatin, and 100 µg atorvastatin" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 1.05397E-06, "NaN", "NaN", 3.84880082E-07, 6.304204E-06, 1.709629E-06, 1.68889E-06, 1.58605008E-06, 5.677239E-06, 7.295083E-06 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 5E-13 }, "Values": [ 5.179475E-05, 4.04709026E-05, 2.912633E-05, 1.8914101E-05, 1.279802E-05, 5.287061E-06, 3.964736E-06, 2.184166E-06, 3.16227784E-06, 2.91263314E-06 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 16.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 2021.0 }, { "Name": "Study Id", "Value": "Quinney 2008" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17635500" }, { "Name": "Source", "Value": "Table 2; Figure 3" }, { "Name": "Grouping", "Value": "Control iv Midazolam All" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Whole Blood" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "0.05 mg/kg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0144191394, 0.01520694, 0.0202972386, 0.01054942, 0.006257259, 0.00703594228, 0.005673063, 0.0047248113, 0.004153073, 0.00429735, 0.002935671, 0.002562531, 0.002152225, 0.001847111 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-09 }, "Values": [ 0.02070937, 0.03830143, 0.05527966, 0.0325954519, 0.02599538, 0.01841642, 0.01485005, 0.0123678595, 0.01087128, 0.009058303, 0.005123824, 0.003407151, 0.002934951, 0.002395514 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.08, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 2024.0 }, { "Name": "Study Id", "Value": "Quinney 2008" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17635500" }, { "Name": "Source", "Value": "Table 2; Figure 3" }, { "Name": "Grouping", "Value": "Control po Midazolam All" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 16.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Whole Blood" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "3.0 - 4.0 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "oral solution" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.005884427, 0.004286726, 0.00320011214, 0.002933298, 0.002313306, 0.00284133921, 0.00238476484, 0.002099898, 0.00203032512, 0.00196832186, 0.00161687192, 0.00138024706 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)|ObservedData|Peripheral Venous Blood|Whole Blood|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-09 }, "Values": [ 0.006068511, 0.007286541, 0.006335396, 0.00620051846, 0.00562823145, 0.005449456, 0.00430080248, 0.003468099, 0.002707789, 0.001389617, 0.00130274007, 0.000874904566 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 361.0 }, { "Name": "Study Id", "Value": "Okudaira 2007" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/17585116" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "EM 0 Control (Perpetrator Placebo)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "5 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum, injectable solution; Astellas Pharma Inc" }, { "Name": "Food state", "Value": "Fed" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.001030928, 0.001082475, 0.001082475, 0.001082475, 0.001082475, 0.001082474, 0.001030928, 0.0009793811, 0.001082474 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.008247422, 0.0160824731, 0.01742268, 0.01742268, 0.0160824731, 0.01072165, 0.00453608157, 0.00257732021, 0.00123711338 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.33, 0.66, 1.0, 1.5, 2.0, 3.0, 5.0, 8.0, 14.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1090.0 }, { "Name": "Study Id", "Value": "Shin 2013" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/23784264" }, { "Name": "Source", "Value": "Table 1" }, { "Name": "Grouping", "Value": "Control phase (Midazolam alone)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 24.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Bukwang Pharmaceutical, Seoul, Korea" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 0.01843485, 0.00815789, 0.00505059632, 0.003483336, 0.002644324, 0.001351647, 0.0008887652, 0.0004129435, 0.000209082791 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.166666672, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1093.0 }, { "Name": "Study Id", "Value": "Shin 2016" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/27317471" }, { "Name": "Source", "Value": "Suppl. Fig. 2; Table 1" }, { "Name": "Grouping", "Value": "Midazolam alone" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Bukwang Pharmaceutical, Seoul, Korea" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.003215254, 0.002364677, 0.00184094, 0.001554821, 0.001652093, 0.00112819, 0.000861464941, 0.000576480641, 0.000398489, 0.0003708317, 0.0002043347, 4.099E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 0.0273258314, 0.02009695, 0.01564583, 0.0121805593, 0.009924419, 0.005307334, 0.003604433, 0.00271193, 0.001417637, 0.00111186609, 0.000545559567, 0.0001395523 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.17, 0.33, 0.5, 0.75, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1107.0 }, { "Name": "Study Id", "Value": "Backman 1994" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/8198928" }, { "Name": "Source", "Value": "Fig. 1; Table 1" }, { "Name": "Grouping", "Value": "Midazolam with placebo" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 9.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "15 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "1x Dormicum 15 mg tablets, Hoffmann-La Roche Ltd, Basel, Switzerland)" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-09 }, "Values": [ 0.04997086, 0.04285479, 0.0387980379, 0.03338099, 0.02356628, 0.0154517, 0.01073514, 0.009074614, 0.007416286, 0.00203771912 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 17.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 2040.0 }, { "Name": "Study Id", "Value": "Katzenmaier 2010" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/20680253" }, { "Name": "Source", "Value": "Figure 1" }, { "Name": "Grouping", "Value": "Midazolam control" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "3 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum" }, { "Name": "Food state", "Value": "fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.02411347, 0.01829787, 0.01687943, 0.016595751, 0.01333333, 0.009503546, 0.00765957031, 0.0043971627, 0.003829787, 0.00283688, "NaN", "NaN" ], "Dimension": "Concentration (molar)", "Unit": "µmol/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 0.0002 }, "Values": [ 0.03702128, 0.0510638319, 0.04241135, 0.03503546, 0.02539007, 0.01858156, 0.01517731, 0.009929078, 0.006666667, 0.00368794287, 0.002411348, 0.001985816 ], "Dimension": "Concentration (molar)", "Unit": "µmol/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 10.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 2042.0 }, { "Name": "Study Id", "Value": "Mikus 2017" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/28194792" }, { "Name": "Source", "Value": "Figure 2" }, { "Name": "Grouping", "Value": "Midazolam control PO" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "4 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "Dormicum" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0104360105, 0.0154571114, 0.007088612, 0.00393811, 0.004036564, 0.003052037, 0.002067511, 0.001575246, 0.001181434, 0.0007876232 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.008663854, 0.02579465, 0.0247116685, 0.0199859422, 0.01624473, 0.01151899, 0.008073136, 0.00511955, 0.003642757, 0.00246132212 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.1666667, 0.3333333, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 2043.0 }, { "Name": "Study Id", "Value": "Mikus 2017" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/28194792" }, { "Name": "Source", "Value": "Figure 2" }, { "Name": "Grouping", "Value": "Midazolam control IV" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 12.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 6.0 }, { "Name": "Formulation", "Value": "Solution" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.0006891696, 0.00777777471, 0.009943741, 0.00630097836, 0.00492263958, 0.004036568, 0.004430378, 0.00364275416, 0.002264418, 0.00167369912, 0.000984529, 0.00167369912, 0.0007876232 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.002067511, 0.0364275724, 0.05296765, 0.03189874, 0.02648383, 0.0221519, 0.01841069, 0.01663854, 0.01270042, 0.008959212, 0.00580872037, 0.00423347345, 0.00246132212 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 6.0, 6.25, 6.5, 6.66666651, 6.83333349, 7.0, 7.25, 7.5, 8.0, 9.0, 10.0, 12.0, 14.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Yu 2004 - Control CYP3A5*1/*1 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 194.0 }, { "Name": "Study Id", "Value": "Yu 2004" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/15289787" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control CYP3A5*1/*1" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Yu 2004 - Control CYP3A5*1/*1 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", "NaN", "NaN", "NaN", "NaN", 0.00163649593, "NaN", 0.0004333923, 0.00042366542, 0.0001455762 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Yu 2004 - Control CYP3A5*1/*1 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 0.0372217223, 0.01399644, 0.01107255, 0.00807383, 0.006789822, 0.004038264, 0.002798354, 0.001010241, 0.0006789823, 0.0003647093 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Yu 2004 - Control CYP3A5*1/*1 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.167, 0.333, 0.5, 0.75, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Yu 2004 - Control CYP3A5*1/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 195.0 }, { "Name": "Study Id", "Value": "Yu 2004" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/15289787" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control CYP3A5*1/*3" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 6.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Yu 2004 - Control CYP3A5*1/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 0.041213952, 0.01842836, 0.01238569, 0.008240038, 0.00510463351, 0.00242636283, 0.00145786291, 0.000744185934, 0.0005209717 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Yu 2004 - Control CYP3A5*1/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.167, 0.333, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 196.0 }, { "Name": "Study Id", "Value": "Yu 2004" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/15289787" }, { "Name": "Source", "Value": "Fig. 1" }, { "Name": "Grouping", "Value": "Control CYP3A5*3/*3" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 7.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "IV" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 0.0495097, 0.0169859, 0.01399644, 0.0103103705, 0.008849173, 0.0050528897, 0.002885207, 0.001565634, 0.001277011, 0.00082400383 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.167, 0.333, 0.5, 0.75, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 203.0 }, { "Name": "Study Id", "Value": "Wiesinger 2020" }, { "Name": "Reference", "Value": "https://www.ncbi.nlm.nih.gov/pubmed/32275771" }, { "Name": "Source", "Value": "https://github.com/Open-Systems-Pharmacology/Hormonal-Contraceptive-Agents-Datasets" }, { "Name": "Grouping", "Value": "Control phase (no RIF)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 65.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "solution (0.5 mL)" }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Name": "Avg", "Path": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|Median" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00458, 0.00399999972, 0.00277, 0.00198, 0.0014, 0.00113, 0.000933, 0.000771, 0.00051, 0.000395, 0.000281000015, 0.000165, 0.000119000004, 3.93E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 8.0, 12.0, 15.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1361.0 }, { "Name": "Study Id", "Value": "Chattopadhyay 2018" }, { "Name": "Reference", "Value": "https://pubmed.ncbi.nlm.nih.gov/30171692/" }, { "Name": "Source", "Value": "Figure 2B" }, { "Name": "Grouping", "Value": "Control (without Rifampicin)" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 11.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "1 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "." }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "GeometricStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 1.47672117, 1.40222168, 1.34634972, 1.25682414, 1.36818516, 1.29426432, 1.42600763, 1.372275, 1.42773032, 1.40022421, 1.47645831, 1.6943742, 1.89271784, 1.841591, 1.88962185 ], "Dimension": "Dimensionless" } ], "QuantityInfo": { "Name": "Avg", "Path": "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|GeometricMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 2E-12 }, "Values": [ 0.003144234, 0.00255575683, 0.00168580329, 0.00123630755, 0.00100116257, 0.000781851239, 0.00066966156, 0.000597655657, 0.00047063813, 0.000382138271, 0.000335310877, 0.000230253674, 0.000138632764, 0.000113536516, 4.73631226E-05 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 4.5, 5.0, 6.0, 8.0, 12.0, 15.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1348.0 }, { "Name": "Study Id", "Value": "Lutz 2018" }, { "Name": "Reference", "Value": "https://pubmed.ncbi.nlm.nih.gov/29569723/" }, { "Name": "Source", "Value": "Fig. 1B" }, { "Name": "Grouping", "Value": "Cohort 1, Control" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 20.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ 0.00277263415, "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN", "NaN" ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 0.004250431, 0.00949255, 0.01160434, 0.01014991, 0.006641926, 0.00459577376, 0.001840532, 0.000704923761, 0.000398996723 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE" }, { "Name": "ID", "Value": 1349.0 }, { "Name": "Study Id", "Value": "Lutz 2018" }, { "Name": "Reference", "Value": "https://pubmed.ncbi.nlm.nih.gov/29569723/" }, { "Name": "Source", "Value": "Fig. 1B" }, { "Name": "Grouping", "Value": "Cohort 2, Control" }, { "Name": "Data type", "Value": "aggregated" }, { "Name": "N", "Value": 20.0 }, { "Name": "Molecule", "Value": "Midazolam" }, { "Name": "Species", "Value": "Human" }, { "Name": "Organ", "Value": "Peripheral Venous Blood" }, { "Name": "Compartment", "Value": "Plasma" }, { "Name": "Route", "Value": "PO" }, { "Name": "Dose", "Value": "2 mg" }, { "Name": "Times of Administration [h]", "Value": 0.0 }, { "Name": "Formulation", "Value": "." }, { "Name": "Food state", "Value": "Fasted" }, { "Name": "Comment", "Value": "." } ], "Columns": [ { "Name": "Avg", "RelatedColumns": [ { "Name": "Var", "QuantityInfo": { "Name": "Var", "Path": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticStdDev" }, "DataInfo": { "Origin": "ObservationAuxiliary", "AuxiliaryType": "ArithmeticStdDev", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77 }, "Values": [ "NaN", 0.004789313, 0.003991857, 0.003276773, 0.00257860078, 0.00217097718, 0.000954948657, 0.000440523581, 0.000263772 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "QuantityInfo": { "Name": "Avg", "Path": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|ObservedData|Peripheral Venous Blood|Plasma|Midazolam|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00", "MolWeight": 325.77, "LLOQ": 1E-10 }, "Values": [ 0.003635646, 0.01037899, 0.01434513, 0.01240794, 0.00839597452, 0.00568123348, 0.002225023, 0.0008617467, 0.000441151817 ], "Dimension": "Concentration (mass)", "Unit": "mg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Name": "Time", "Path": "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined", "Date": "0001-01-01T00:00:00" }, "Values": [ 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 4.0, 8.0, 12.0 ], "Dimension": "Time", "Unit": "h" } } ], "ObservedDataClassifications": [ { "Name": "Allonen 1981", "Classifiables": [ "Allonen 1981 - oral - Midazolam - PO - 15 mg - Plasma - agg. (n=6)", "Allonen 1981 - iv - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=6)" ] }, { "Name": "Backman 1996", "Classifiables": [ "Backman 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=10)" ] }, { "Name": "Backman 1998", "Classifiables": [ "Backman 1998 - Phase I (Control (Perpetrator Placebo)) - Midazolam - PO - 15 mg - Plasma - agg. (n=9)" ] }, { "Name": "Chung 2006", "Classifiables": [ "Chung 2006 - Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg/kg - Plasma - agg. (n=18)" ] }, { "Name": "Darwish 2008", "Classifiables": [ "Darwish 2008 - iv - Midazolam - IV - 2 mg - Plasma - agg. (n=24)", "Darwish 2008 - oral - Midazolam - PO - 5 mg - Plasma - agg. (n=24)" ] }, { "Name": "Gorski 1998", "Classifiables": [ "Gorski 1998 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=16)", "Gorski 1998 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)" ] }, { "Name": "Gorski 2003", "Classifiables": [ "Gorski 2003 - po Control (Perpetrator Placebo) - Midazolam - PO - 4 mg - Whole Blood - agg. (n=52)", "Gorski 2003 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=52)" ] }, { "Name": "Greenblat 1984", "Classifiables": [ "Greenblat 1984 - iv - f, 136kg, 36y (obese female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)", "Greenblat 1984 - iv - f, 61kg, 37y (normal female) - Midazolam - IV - 5 mg - Plasma - typical (n=10)", "Greenblat 1984 - iv - m, 70kg, 32y (young male) - Midazolam - IV - 5 mg - Plasma - typical (n=10)", "Greenblat 1984 - iv - m, 80kg, 70y (elderly male) - Midazolam - IV - 5 mg - Plasma - typical (n=9)", "Greenblat 1984 - po - f, 136kg, 36y (obese female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)", "Greenblat 1984 - po - f, 61kg, 37y (normal female) - Midazolam - PO - 10 mg - Plasma - typical (n=10)", "Greenblat 1984 - po - m, 70kg, 32y (young male) - Midazolam - PO - 10 mg - Plasma - typical (n=10)", "Greenblat 1984 - po - m, 80kg, 70y (elderly male) - Midazolam - PO - 10 mg - Plasma - typical (n=9)" ] }, { "Name": "Greenblat 2003", "Classifiables": [ "Greenblat 2003 - Control (Perpetrator Placebo) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)", "Greenblat 2003 - with Perpetrator (GFJ) - Midazolam - PO - 6 mg - Plasma - agg. (n=25)" ] }, { "Name": "Gurley 2006", "Classifiables": [ "Gurley 2006 - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "Gurley 2006 - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "Gurley 2006 - Control pre-Black cohosh (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)", "Gurley 2006 - Control pre-Milk thistle (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=19)" ] }, { "Name": "Gurley 2008a", "Classifiables": [ "Gurley 2008a - Control pre-Rifampicin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "Gurley 2008a - Control pre-Clarithromycin (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "Gurley 2008a - Control pre-Goldenseal (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)", "Gurley 2008a - Control pre-Kava kava (Perpetrator Placebo) - Midazolam - PO - 8 mg - Plasma - agg. (n=16)" ] }, { "Name": "Heizmann 1983", "Classifiables": [ "Heizmann 1983 - iv 0.15 mg/kg - Indiv. CH.B. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. K.M. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. E.Sch. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. R.H. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. A.St. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - iv 0.15 mg/kg - Indiv. O.A. - Midazolam - IV - 0.15 mg/kg - Plasma - indiv.", "Heizmann 1983 - po 10 mg - Indiv. K.M. - Midazolam - PO - 10 mg - Plasma - indiv.", "Heizmann 1983 - po 10 mg - Indiv. O.A. - Midazolam - PO - 10 mg - Plasma - indiv.", "Heizmann 1983 - po 10 mg - Indiv. R.H. - Midazolam - PO - 10 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. A.St. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. CH.B. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. E.Sch. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. K.M. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. O.A. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 20 mg - Indiv. R.H. - Midazolam - PO - 20 mg - Plasma - indiv.", "Heizmann 1983 - po 40 mg - Indiv. A.St. - Midazolam - PO - 40 mg - Plasma - indiv.", "Heizmann 1983 - po 40 mg - Indiv. CH.B. - Midazolam - PO - 40 mg - Plasma - indiv.", "Heizmann 1983 - po 40 mg - Indiv. E.Sch. - Midazolam - PO - 40 mg - Plasma - indiv." ] }, { "Name": "Hohmann 2015", "Classifiables": [ "Hohmann 2015 - iv 0.001 mg - Midazolam - IV - 0.001 mg - Plasma - agg. (n=16)", "Hohmann 2015 - iv 1 mg - Midazolam - IV - 1 mg - Plasma - agg. (n=16)", "Hohmann 2015 - po 0.003 mg - Midazolam - PO - 0.003 mg - Plasma - agg. (n=16)", "Hohmann 2015 - po 3 mg - Midazolam - PO - 3 mg - Plasma - agg. (n=16)" ] }, { "Name": "Hyland 2009", "Classifiables": [ "Hyland 2009 - 3-mg oral dose (as fraction of dose) - Midazolam-N-Glucuronide - PO - 3 mg - Urine - agg. (n=6)", "Hyland 2009 - 1-mg i.v. dose (as fraction of dose) - Midazolam-N-Glucuronide - IV - 1 mg - Urine - agg. (n=6)" ] }, { "Name": "Kharasch 1997", "Classifiables": [ "Kharasch 1997 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - typical (n=9)" ] }, { "Name": "Kharasch 2004", "Classifiables": [ "Kharasch 2004 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=10)", "Kharasch 2004 - po #1 Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=10)" ] }, { "Name": "Kharasch 2011", "Classifiables": [ "Kharasch 2011 - po Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=12)", "Kharasch 2011 - iv Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=12)" ] }, { "Name": "Link 2008", "Classifiables": [ "Link 2008 - iv Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=8)", "Link 2008 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=8)" ] }, { "Name": "Majumdar 2007", "Classifiables": [ "Majumdar 2007 - po Control (Perpetrator Placebo) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)", "Majumdar 2007 - po with Perpetrator (Aprepitant) - Midazolam - IV - 2 mg - Plasma - agg. (n=12)" ] }, { "Name": "Okudaira 2007", "Classifiables": [ "Okudaira 2007 - EM 0 Control (Perpetrator Placebo) - Midazolam - PO - 5 mg - Plasma - agg. (n=12)" ] }, { "Name": "Olkkola 1993", "Classifiables": [ "Olkkola 1993 - po Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)", "Olkkola 1993 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=6)" ] }, { "Name": "Olkkola 1994", "Classifiables": [ "Olkkola 1994 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=9)" ] }, { "Name": "Olkkola 1996", "Classifiables": [ "Olkkola 1996 - day 6 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)", "Olkkola 1996 - day 4 (iv) Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=12)", "Olkkola 1996 - day 1 (po) Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)" ] }, { "Name": "Phimmasone 2001", "Classifiables": [ "Phimmasone 2001 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=6)" ] }, { "Name": "Reitman 2011", "Classifiables": [ "Reitman 2011 - Week 4 after Perpetrator (Rifampicin) - Midazolam - PO - 2 mg - Plasma - agg. (n=11)" ] }, { "Name": "Saari 2006", "Classifiables": [ "Saari 2006 - po Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=10)", "Saari 2006 - iv Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=10)" ] }, { "Name": "Schwagmeier 1998", "Classifiables": [ "Schwagmeier 1998 - iv administration - Midazolam - IV - 5 mg - Plasma - agg. (n=8)" ] }, { "Name": "Smith 1981", "Classifiables": [ "Smith 1981 - iv 5 mg - Midazolam - IV - 5 mg - Plasma - agg. (n=6)", "Smith 1981 - oral solution 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)", "Smith 1981 - oral tablet 10 mg - Midazolam - PO - 10 mg - Plasma - agg. (n=6)" ] }, { "Name": "Szalat 2007", "Classifiables": [ "Szalat 2007 - Control (Perpetrator Placebo) - Midazolam - IV - 0.05 mg/kg - Plasma - agg. (n=3)" ] }, { "Name": "Templeton 2010", "Classifiables": [ "Templeton 2010 - Control (Perpetrator Placebo) - Midazolam - PO - 2 mg - Plasma - agg. (n=6)" ] }, { "Name": "Tham 2006", "Classifiables": [ "Tham 2006 - Control (Perpetrator Placebo) - Midazolam - IV - 1 mg - Plasma - agg. (n=28)" ] }, { "Name": "Thummel 1996", "Classifiables": [ "Thummel 1996 - iv - female - Midazolam - IV - 1 mg - Urine - agg. (n=10)", "Thummel 1996 - iv - male - Midazolam - IV - 1 mg - Urine - agg. (n=10)", "Thummel 1996 - po - female - Midazolam - PO - 2 mg - Urine - agg. (n=10)", "Thummel 1996 - po - male - Midazolam - PO - 2 mg - Urine - agg. (n=10)" ] }, { "Name": "Yeates 1996", "Classifiables": [ "Yeates 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)" ] }, { "Name": "Zimmermann 1996", "Classifiables": [ "Zimmermann 1996 - Control (Perpetrator Placebo) - Midazolam - PO - 15 mg - Plasma - agg. (n=12)" ] }, { "Name": "Ahonen 1995", "Classifiables": [ "Ahonen 1995 - Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=12)" ] }, { "Name": "Eap 2004", "Classifiables": [ "Eap 2004 - 7.5 mg Control (Perpetrator Placebo) - Midazolam - PO - 7.5 mg - Plasma - agg. (n=13)", "Eap 2004 - 0.075 mg Control (Perpetrator Placebo) - Midazolam - PO - 0.075 mg - Plasma - agg. (n=21)" ] }, { "Name": "Swart 2002", "Classifiables": [ "Swart 2002 - day 5 Control (Perpetrator Placebo) - Midazolam - IV - 0.075 mg/kg - Plasma - agg. (n=8)" ] }, { "Name": "Bornemann 1986", "Classifiables": [ "Bornemann 1986 - 1 h after a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "Bornemann 1986 - 1 h before a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "Bornemann 1986 - fasting condition - Midazolam - PO - 15 mg - Plasma - agg. (n=18)", "Bornemann 1986 - with a meal - Midazolam - PO - 15 mg - Plasma - agg. (n=18)" ] }, { "Name": "Lam 2003", "Classifiables": [ "Lam 2003 - Midazolam before Fluvoxamine - Midazolam - PO - 10 mg - Plasma - agg. (n=10)", "Lam 2003 - Midazolam before Ketoconazole - Midazolam - PO - 10 mg - Plasma - agg. (n=10)" ] }, { "Name": "van Dyk 2018", "Classifiables": [ "van Dyk 2018 - Midazolam in South Asian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=11)", "van Dyk 2018 - Midazolam in Caucasian at baseline - Midazolam - PO - 1 mg - Plasma - agg. (n=19)" ] }, { "Name": "Markert 2013", "Classifiables": [ "Markert 2013 - Control (Perpetrator Placebo) - Midazolam - PO - 3 mg - Plasma - agg. (n=11)" ] }, { "Name": "Prueksaritanont 2017", "Classifiables": [ "Prueksaritanont 2017 - Midazolam in microdosecocktail alone - Midazolam - PO - 10 µg - Plasma - agg. (n=12)" ] }, { "Name": "Quinney 2008", "Classifiables": [ "Quinney 2008 - Control iv Midazolam All - Midazolam - IV - 0.05 mg/kg - Whole Blood - agg. (n=16)", "Quinney 2008 - Control po Midazolam All - Midazolam - PO - 3.0 - 4.0 mg - Whole Blood - agg. (n=16)" ] }, { "Name": "Shin 2013", "Classifiables": [ "Shin 2013 - Control phase (Midazolam alone) - Midazolam - IV - 1 mg - Plasma - agg. (n=24)" ] }, { "Name": "Shin 2016", "Classifiables": [ "Shin 2016 - Midazolam alone - Midazolam - IV - 1 mg - Plasma - agg. (n=12)" ] }, { "Name": "Backman 1994", "Classifiables": [ "Backman 1994 - Midazolam with placebo - Midazolam - PO - 15 mg - Plasma - agg. (n=9)" ] }, { "Name": "Katzenmaier 2010", "Classifiables": [ "Katzenmaier 2010 - Midazolam control - Midazolam - PO - 3 mg - Plasma - agg. (n=12)" ] }, { "Name": "Mikus 2017", "Classifiables": [ "Mikus 2017 - Midazolam control PO - Midazolam - PO - 4 mg - Plasma - agg. (n=12)", "Mikus 2017 - Midazolam control IV - Midazolam - IV - 2 mg - Plasma - agg. (n=12)" ] }, { "Name": "Yu 2004", "Classifiables": [ "Yu 2004 - Control CYP3A5*1/*1 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", "Yu 2004 - Control CYP3A5*1/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=6)", "Yu 2004 - Control CYP3A5*3/*3 - Midazolam - IV - 1 mg - Plasma - agg. (n=7)" ] }, { "Name": "Wiesinger 2020", "Classifiables": [ "Wiesinger 2020 - Control phase (no RIF) - Midazolam - PO - 1 mg - Plasma - agg. (n=65)" ] }, { "Name": "Chattopadhyay 2018", "Classifiables": [ "Chattopadhyay 2018 - Control (without Rifampicin) - Midazolam - PO - 1 mg - Plasma - agg. (n=11)" ] }, { "Name": "Lutz 2018", "Classifiables": [ "Lutz 2018 - Cohort 1, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)", "Lutz 2018 - Cohort 2, Control - Midazolam - PO - 2 mg - Plasma - agg. (n=20)" ] } ], "SimulationClassifications": [ { "Name": "#PI", "Classifiables": [ "iv 0.001 mg (5 min)", "iv 1 mg (5 min)", "po 0.003 mg (solution)", "po 3 mg (solution)", "po 7.5 mg (tablet)", "iv 1 mg (2 min)" ] }, { "Name": "IV", "Classifiables": [ "iv 0.05 mg/kg (2 min)", "iv 0.05 mg/kg (30 min)", "iv 0.05 mg/kg (bolus)", "iv 0.075 mg/kg (1 min)", "iv 0.15 mg/kg (bolus)", "iv 1 mg (bolus)", "iv 2 mg (2 min)", "iv 2 mg (bolus)", "iv 5 mg (30 sec)", "iv 5 mg (bolus)" ] }, { "Name": "PO", "Classifiables": [ "po 0.075 mg (solution)", "po 0.075 mg/kg (syrup)", "po 1 mg (solution)", "po 10 mg (tablet)", "po 15 mg (tablet)", "po 2 mg (solution)", "po 20 mg (tablet)", "po 4 mg (solution)", "po 40 mg (tablet)", "po 5 mg (solution)", "po 6 mg (solution)", "po 7.5 mg (solution)", "po 8 mg (solution)", "po 10 mg (solution)", "po 15 mg (tablet) - with high-fat breakfast", "po 15 mg (tablet) - with 1 h before high-fat breakfast", "po 15 mg (tablet) - with 1h after high-fat breakfast", "po 2.5 mg (solution)", "po 3.5 mg (solution)", "po 0.01 mg (solution)" ] }, { "Name": "Mixed application", "Classifiables": [ "Mikus 2017" ] } ] }