{ "Version": 79, "ExpressionProfiles": [ { "Type": "Enzyme", "Species": "Human", "Molecule": "CYP3A4", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "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": "Organism|Brain|Intracellular|CYP3A4|Relative expression", "Value": 0.0041682898325 }, { "Path": "Organism|Gonads|Intracellular|CYP3A4|Relative expression", "Value": 0.00078691079081 }, { "Path": "Organism|Kidney|Intracellular|CYP3A4|Relative expression", "Value": 0.0053603428126 }, { "Path": "Organism|Liver|Pericentral|Intracellular|CYP3A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|CYP3A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Lung|Intracellular|CYP3A4|Relative expression", "Value": 0.00042695753798 }, { "Path": "Organism|SmallIntestine|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|CYP3A4|Relative expression", "Value": 0.0727697702 } ], "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome", "Ontogeny": { "Name": "CYP3A4" } }, { "Type": "Enzyme", "Species": "Human", "Molecule": "AADAC", "Category": "European (P-gp modified, CYP3A4 36 h)", "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": "Organism|Bone|Intracellular|AADAC|Relative expression", "Value": 4.8717948718E-05 }, { "Path": "Organism|Brain|Intracellular|AADAC|Relative expression", "Value": 3.9743589744E-05 }, { "Path": "Organism|Gonads|Intracellular|AADAC|Relative expression", "Value": 0.0011923076923 }, { "Path": "Organism|Heart|Intracellular|AADAC|Relative expression", "Value": 0.0026602564103 }, { "Path": "Organism|Kidney|Intracellular|AADAC|Relative expression", "Value": 5.7051282051E-05 }, { "Path": "Organism|LargeIntestine|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|AADAC|Relative expression", "Value": 0.00010384615385 }, { "Path": "Organism|Liver|Pericentral|Intracellular|AADAC|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|AADAC|Relative expression", "Value": 1.0 }, { "Path": "Organism|Lung|Intracellular|AADAC|Relative expression", "Value": 0.0269230769 }, { "Path": "Organism|Muscle|Intracellular|AADAC|Relative expression", "Value": 0.00020833333333 }, { "Path": "Organism|Pancreas|Intracellular|AADAC|Relative expression", "Value": 0.1474358974 }, { "Path": "Organism|SmallIntestine|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|AADAC|Relative expression", "Value": 0.2544871795 }, { "Path": "Organism|Spleen|Intracellular|AADAC|Relative expression", "Value": 0.00037115384615 }, { "Path": "Organism|Stomach|Intracellular|AADAC|Relative expression", "Value": 0.0775641026 } ], "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome" }, { "Type": "Transporter", "Species": "Human", "Molecule": "P-gp", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "Path": "Organism|Bone|Intracellular|P-gp|Relative expression", "Value": 0.0242518189 }, { "Path": "Organism|Brain|Intracellular|P-gp|Relative expression", "Value": 0.07608904 }, { "Path": "Organism|Gonads|Intracellular|P-gp|Relative expression", "Value": 0.017417973 }, { "Path": "Organism|Heart|Intracellular|P-gp|Relative expression", "Value": 0.0419198106 }, { "Path": "Organism|Kidney|Intracellular|P-gp|Relative expression", "Value": 0.7092198582 }, { "Path": "Organism|LargeIntestine|Intracellular|P-gp|Relative expression", "Value": 0.1108416465 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|P-gp|Relative expression", "Value": 0.3971631206 }, { "Path": "Organism|Liver|Pericentral|Intracellular|P-gp|Relative expression", "Value": 0.1916810428 }, { "Path": "Organism|Liver|Periportal|Intracellular|P-gp|Relative expression", "Value": 0.1916810428 }, { "Path": "Organism|Lung|Intracellular|P-gp|Relative expression", "Value": 0.0657549316 }, { "Path": "Organism|Muscle|Intracellular|P-gp|Relative expression", "Value": 0.0128342959 }, { "Path": "Organism|Pancreas|Intracellular|P-gp|Relative expression", "Value": 0.0142510689 }, { "Path": "Organism|SmallIntestine|Intracellular|P-gp|Relative expression", "Value": 0.2808543974 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|P-gp|Relative expression", "Value": 1.0 }, { "Path": "Organism|Spleen|Intracellular|P-gp|Relative expression", "Value": 0.0742555691 }, { "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" } ], "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 } ] } } }, { "Type": "Transporter", "Species": "Human", "Molecule": "OATP1B1", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "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|Brain|Intracellular|OATP1B1|Relative expression", "Value": 0.00014166666667 }, { "Path": "Organism|Gonads|Intracellular|OATP1B1|Relative expression", "Value": 0.0141666667 }, { "Path": "Organism|Heart|Intracellular|OATP1B1|Relative expression", "Value": 0.0008253968254 }, { "Path": "Organism|Liver|Pericentral|Intracellular|OATP1B1|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|OATP1B1|Relative expression", "Value": 1.0 }, { "Path": "Organism|Lung|Intracellular|OATP1B1|Relative expression", "Value": 4.0079365079E-05 }, { "Path": "Organism|Muscle|Intracellular|OATP1B1|Relative expression", "Value": 0.00064682539683 } ], "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" } ] }, { "Type": "OtherProtein", "Species": "Human", "Molecule": "ATP1A2", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "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": "Organism|Bone|Intracellular|ATP1A2|Relative expression", "Value": 0.0062154033171 }, { "Path": "Organism|Brain|Intracellular|ATP1A2|Relative expression", "Value": 1.0 }, { "Path": "Organism|Gonads|Intracellular|ATP1A2|Relative expression", "Value": 0.0508741242 }, { "Path": "Organism|Heart|Intracellular|ATP1A2|Relative expression", "Value": 0.3179118843 }, { "Path": "Organism|Kidney|Intracellular|ATP1A2|Relative expression", "Value": 0.0158938619 }, { "Path": "Organism|LargeIntestine|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonAscendens|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonDescendens|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonSigmoid|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|LargeIntestine|Mucosa|ColonTransversum|Intracellular|ATP1A2|Relative expression", "Value": 0.0786998764 }, { "Path": "Organism|Liver|Pericentral|Intracellular|ATP1A2|Relative expression", "Value": 0.0223784807 }, { "Path": "Organism|Liver|Periportal|Intracellular|ATP1A2|Relative expression", "Value": 0.0223784807 }, { "Path": "Organism|Lung|Intracellular|ATP1A2|Relative expression", "Value": 0.0272345453 }, { "Path": "Organism|Muscle|Intracellular|ATP1A2|Relative expression", "Value": 0.7034193524 }, { "Path": "Organism|Pancreas|Intracellular|ATP1A2|Relative expression", "Value": 0.0073903254795 }, { "Path": "Organism|Skin|Intracellular|ATP1A2|Relative expression", "Value": 0.0389467988 }, { "Path": "Organism|SmallIntestine|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|ATP1A2|Relative expression", "Value": 0.0501579923 }, { "Path": "Organism|Spleen|Intracellular|ATP1A2|Relative expression", "Value": 0.0103243118 }, { "Path": "Organism|Stomach|Intracellular|ATP1A2|Relative expression", "Value": 0.0309435884 } ], "Localization": "Interstitial, BloodCellsMembrane, VascMembranePlasmaSide" }, { "Type": "Enzyme", "Species": "Human", "Molecule": "UGT1A4", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "Path": "Organism|Liver|Pericentral|Intracellular|UGT1A4|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|UGT1A4|Relative expression", "Value": 1.0 }, { "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" } ], "Localization": "Intracellular, BloodCellsIntracellular, VascEndosome", "Ontogeny": { "Name": "UGT1A4" } }, { "Type": "OtherProtein", "Species": "Human", "Molecule": "GABRG2", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "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": "Organism|Brain|Intracellular|GABRG2|Relative expression", "Value": 1.0 } ], "Localization": "Interstitial, BloodCellsMembrane, VascMembranePlasmaSide" }, { "Type": "Enzyme", "Species": "Human", "Molecule": "CYP2C9", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "Path": "CYP2C9|Reference concentration", "Value": 3.84, "Unit": "µmol/l" }, { "Path": "CYP2C9|t1/2 (intestine)", "Value": 1380.0, "Unit": "min" }, { "Path": "CYP2C9|t1/2 (liver)", "Value": 6240.0, "Unit": "min" }, { "Path": "Organism|Brain|Intracellular|CYP2C9|Relative expression", "Value": 0.00039687350455 }, { "Path": "Organism|Gonads|Intracellular|CYP2C9|Relative expression", "Value": 4.5940341362E-05 }, { "Path": "Organism|Kidney|Intracellular|CYP2C9|Relative expression", "Value": 0.0018822778753 }, { "Path": "Organism|Liver|Pericentral|Intracellular|CYP2C9|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|CYP2C9|Relative expression", "Value": 1.0 }, { "Path": "Organism|Lung|Intracellular|CYP2C9|Relative expression", "Value": 0.0002131121391 }, { "Path": "Organism|SmallIntestine|Intracellular|CYP2C9|Relative expression", "Value": 0.1199553358 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|CYP2C9|Relative expression", "Value": 0.1199553358 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|CYP2C9|Relative expression", "Value": 0.1199553358 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|CYP2C9|Relative expression", "Value": 0.1199553358 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|CYP2C9|Relative expression", "Value": 0.1199553358 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|CYP2C9|Relative expression", "Value": 0.1199553358 } ], "Localization": "Intracellular", "Ontogeny": { "Name": "CYP2C9" } }, { "Type": "Enzyme", "Species": "Human", "Molecule": "CYP2C19", "Category": "European (P-gp modified, CYP3A4 36 h)", "Parameters": [ { "Path": "CYP2C19|Reference concentration", "Value": 0.76, "Unit": "µmol/l" }, { "Path": "CYP2C19|t1/2 (intestine)", "Value": 1380.0, "Unit": "min" }, { "Path": "CYP2C19|t1/2 (liver)", "Value": 1560.0, "Unit": "min" }, { "Path": "Organism|Brain|Intracellular|CYP2C19|Relative expression", "Value": 0.00014961101137 }, { "Path": "Organism|Gonads|Intracellular|CYP2C19|Relative expression", "Value": 0.0003526545268 }, { "Path": "Organism|Kidney|Intracellular|CYP2C19|Relative expression", "Value": 0.00015816021202 }, { "Path": "Organism|Liver|Pericentral|Intracellular|CYP2C19|Relative expression", "Value": 1.0 }, { "Path": "Organism|Liver|Periportal|Intracellular|CYP2C19|Relative expression", "Value": 1.0 }, { "Path": "Organism|Lung|Intracellular|CYP2C19|Relative expression", "Value": 0.00040608703086 }, { "Path": "Organism|SmallIntestine|Intracellular|CYP2C19|Relative expression", "Value": 0.3238009746 }, { "Path": "Organism|SmallIntestine|Mucosa|Duodenum|Intracellular|CYP2C19|Relative expression", "Value": 0.3238009746 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerIleum|Intracellular|CYP2C19|Relative expression", "Value": 0.3238009746 }, { "Path": "Organism|SmallIntestine|Mucosa|LowerJejunum|Intracellular|CYP2C19|Relative expression", "Value": 0.3238009746 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperIleum|Intracellular|CYP2C19|Relative expression", "Value": 0.3238009746 }, { "Path": "Organism|SmallIntestine|Mucosa|UpperJejunum|Intracellular|CYP2C19|Relative expression", "Value": 0.3238009746 } ], "Localization": "Intracellular", "Ontogeny": { "Name": "CYP2C19" } } ], "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": "Organism|Liver|EHC continuous fraction", "Value": 1.0, "ValueOrigin": { "Source": "Unknown" } } ], "ExpressionProfiles": [ "CYP3A4|Human|European (P-gp modified, CYP3A4 36 h)", "AADAC|Human|European (P-gp modified, CYP3A4 36 h)", "P-gp|Human|European (P-gp modified, CYP3A4 36 h)", "OATP1B1|Human|European (P-gp modified, CYP3A4 36 h)", "ATP1A2|Human|European (P-gp modified, CYP3A4 36 h)", "UGT1A4|Human|European (P-gp modified, CYP3A4 36 h)", "GABRG2|Human|European (P-gp modified, CYP3A4 36 h)", "CYP2C9|Human|European (P-gp modified, CYP3A4 36 h)", "CYP2C19|Human|European (P-gp modified, CYP3A4 36 h)" ] } ], "Compounds": [ { "Name": "Erythromycin", "IsSmallMolecule": true, "Lipophilicity": [ { "Name": "Literature (average value)", "Parameters": [ { "Name": "Lipophilicity", "Value": 2.82, "Unit": "Log Units", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } } ] } ], "FractionUnbound": [ { "Name": "Barre 1987", "Species": "Human", "Parameters": [ { "Name": "Fraction unbound (plasma, reference value)", "Value": 0.305, "ValueOrigin": { "Source": "Publication", "Method": "InVivo", "Description": "PMID: 3606934" } } ] } ], "Solubility": [ { "Name": "Erythromycin stearate film-coated tablet", "Parameters": [ { "Name": "Solubility at reference pH", "Value": 28.0708790976, "Unit": "mg/l", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from '003 - BP conc ratio FIX' on 2019-11-14 14:43" } }, { "Name": "Reference pH", "Value": 7.0, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from '001' on 2019-10-01 13:46" } } ] }, { "Name": "Erythromycin base enteric coated pellets", "IsDefault": false, "Parameters": [ { "Name": "Solubility at reference pH", "Value": 500.0, "Unit": "mg/l", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from '001' on 2019-10-01 13:46" } }, { "Name": "Reference pH", "Value": 7.0, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from '001' on 2019-10-01 13:46" } } ] }, { "Name": "Erythromycin lactobionate", "IsDefault": false, "Parameters": [ { "Name": "Solubility at reference pH", "Value": 200.0, "Unit": "mg/ml", "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Hoffhine, Jr Charles E. \"Aqueous soluble salts of erythromycin.\" U.S. Patent 2,761,859, issued September 4, 1956. " } }, { "Name": "Reference pH", "Value": 7.0, "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Hoffhine, Jr Charles E. \"Aqueous soluble salts of erythromycin.\" U.S. Patent 2,761,859, issued September 4, 1956. " } } ] }, { "Name": "Erythromycin base enteric coated tablet", "IsDefault": false, "Parameters": [ { "Name": "Solubility at reference pH", "Value": 8.3990771997, "Unit": "mg/l", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } }, { "Name": "Reference pH", "Value": 7.0 } ] } ], "IntestinalPermeability": [ { "Name": "Fitted", "Parameters": [ { "Name": "Specific intestinal permeability (transcellular)", "Value": 0.00038668371665, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } } ] } ], "PkaTypes": [ { "Type": "Base", "Pka": 8.88, "ValueOrigin": { "Source": "Publication", "Method": "Unknown", "Description": "PMID: 9135031" } } ], "Processes": [ { "InternalName": "MetabolizationLiverMicrosomes_MM", "DataSource": "Biotransformation_fitted", "Molecule": "CYP3A4", "Parameters": [ { "Name": "In vitro Vmax for liver microsomes", "Value": 918.33333, "Unit": "pmol/min/mg mic. protein", "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "PMID: 9566442" } }, { "Name": "Km", "Value": 70.0, "Unit": "µM", "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "Average of reported values in the literature (PMID: 9107550 and PMID: 9566442)" } } ] }, { "InternalName": "GlomerularFiltration", "DataSource": "fitted", "Species": "Human", "Parameters": [ { "Name": "GFR fraction", "Value": 1.1591081815, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } } ] }, { "InternalName": "IrreversibleInhibition", "DataSource": "MBI", "Molecule": "CYP3A4", "Parameters": [ { "Name": "kinact", "Value": 0.0296261146, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } }, { "Name": "K_kinact_half", "Value": 7.6007360452, "Unit": "µmol/l", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } } ] }, { "InternalName": "ActiveTransportSpecific_MM", "DataSource": "fitted", "Molecule": "OATP1B1", "Parameters": [ { "Name": "Transporter concentration", "Value": 1.0, "Unit": "µmol/l" }, { "Name": "Vmax", "Value": 11.66, "Unit": "pmol/ml/min", "ValueOrigin": { "Source": "Publication", "Method": "InVitro", "Description": "PMID: 22990751" } }, { "Name": "Km", "Value": 0.735836485, "Unit": "µmol/l", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } }, { "Name": "kcat", "Value": 1.350032201, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } } ] }, { "InternalName": "LiverClearance", "DataSource": "fitted", "Species": "Human", "Parameters": [ { "Name": "Fraction unbound (experiment)", "Value": 0.305 }, { "Name": "Lipophilicity (experiment)", "Value": 2.48, "Unit": "Log Units" }, { "Name": "Plasma clearance", "Value": 0.0, "Unit": "ml/min/kg" }, { "Name": "Specific clearance", "Value": 4.1462183378, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } } ] } ], "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - Charge dependent Schmitt" ], "Parameters": [ { "Name": "Molecular weight", "Value": 733.927, "Unit": "g/mol", "ValueOrigin": { "Source": "Internet", "Description": "drugbank.ca" } } ] }, { "Name": "Sildenafil", "IsSmallMolecule": true, "PlasmaProteinBindingPartner": "Glycoprotein", "Lipophilicity": [ { "Name": "Measurement", "Parameters": [ { "Name": "Lipophilicity", "Value": 2.8411110506, "Unit": "Log Units", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } } ] } ], "FractionUnbound": [ { "Name": "Measurement", "Species": "Human", "Parameters": [ { "Name": "Fraction unbound (plasma, reference value)", "Value": 0.04, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } } ] } ], "Solubility": [ { "Name": "Measurement", "Parameters": [ { "Name": "Solubility at reference pH", "Value": 3.5, "Unit": "mg/l", "ValueOrigin": { "Source": "Publication", "Description": "Salerno 2021" } }, { "Name": "Reference pH", "Value": 7.0, "ValueOrigin": { "Source": "Publication", "Description": "Salerno 2021" } } ] }, { "Name": "Oral solution", "IsDefault": false, "Parameters": [ { "Name": "Solubility at reference pH", "Value": 100.0, "Unit": "mg/l", "ValueOrigin": { "Source": "Other", "Method": "Assumption" } }, { "Name": "Reference pH", "Value": 7.0, "ValueOrigin": { "Source": "Other", "Method": "Assumption" } } ] } ], "IntestinalPermeability": [ { "Name": "Optimized", "Parameters": [ { "Name": "Specific intestinal permeability (transcellular)", "Value": 0.00044843836067, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } } ] } ], "Permeability": [ { "Name": "Optimized", "Parameters": [ { "Name": "Permeability", "Value": 0.0758702742, "Unit": "cm/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } } ] } ], "PkaTypes": [ { "Type": "Base", "Pka": 5.97, "ValueOrigin": { "Source": "Publication", "Description": "Salerno 2021" } } ], "Processes": [ { "InternalName": "rCYP450_MM", "DataSource": "Warrington", "Molecule": "CYP2C19", "Parameters": [ { "Name": "In vitro Vmax/recombinant enzyme", "Value": 0.01009105, "Unit": "pmol/min/pmol rec. enzyme", "ValueOrigin": { "Source": "Publication", "Description": "Warrington 2000" } }, { "Name": "Km", "Value": 23.1, "Unit": "µmol/l", "ValueOrigin": { "Source": "Publication", "Description": "Warrington 2000" } }, { "Name": "kcat", "Value": 1.777778489, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } } ] }, { "InternalName": "rCYP450_MM", "DataSource": "Warrington", "Molecule": "CYP2C9", "Parameters": [ { "Name": "In vitro Vmax/recombinant enzyme", "Value": 0.02, "Unit": "pmol/min/pmol rec. enzyme", "ValueOrigin": { "Source": "Publication", "Description": "Warrington 2000" } }, { "Name": "Km", "Value": 9.6, "Unit": "µmol/l", "ValueOrigin": { "Source": "Publication", "Description": "Warrington 2000" } }, { "Name": "kcat", "Value": 3.5234757314, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } } ] }, { "InternalName": "rCYP450_MM", "DataSource": "Warrington", "Molecule": "CYP3A4", "Parameters": [ { "Name": "In vitro Vmax/recombinant enzyme", "Value": 0.16918611, "Unit": "pmol/min/pmol rec. enzyme", "ValueOrigin": { "Source": "Publication", "Description": "Warrington 2000" } }, { "Name": "Km", "Value": 23.1, "Unit": "µmol/l", "ValueOrigin": { "Source": "Publication", "Description": "Warrington 2000" } }, { "Name": "kcat", "Value": 29.8061576339, "Unit": "1/min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } } ] } ], "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Parameters": [ { "Name": "Molecular weight", "Value": 474.58, "Unit": "g/mol", "ValueOrigin": { "Source": "Internet", "Description": "DrugBank DB00203" } } ] } ], "Formulations": [ { "Name": "Sildenafil Tablet", "FormulationType": "Formulation_Tablet_Weibull", "Parameters": [ { "Name": "Dissolution time (50% dissolved)", "Value": 4.164698, "Unit": "min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } }, { "Name": "Lag time", "Value": 0.0, "Unit": "min" }, { "Name": "Dissolution shape", "Value": 1.37405, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'PI_All_DissoKineticFit' on 2022-08-12 15:40" } }, { "Name": "Use as suspension", "Value": 1.0 } ] }, { "Name": "Erythromycin_Weibull_filmtablet", "FormulationType": "Formulation_Tablet_Weibull", "Parameters": [ { "Name": "Dissolution time (50% dissolved)", "Value": 1.7038947098, "Unit": "min", "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } }, { "Name": "Lag time", "Value": 0.0, "Unit": "min", "ValueOrigin": { "Source": "Other", "Method": "Assumption" } }, { "Name": "Dissolution shape", "Value": 1.0960212213, "ValueOrigin": { "Source": "ParameterIdentification", "Method": "ParameterIdentification", "Description": "Value updated from 'Parameter Identification 1' on 2020-01-13 15:01" } }, { "Name": "Use as suspension", "Value": 1.0 } ] } ], "Protocols": [ { "Name": "Muirhead2002_Treatment_Erythromycin_PO_500mg_BID", "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": 500.0, "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": 10.0, "ValueOrigin": { "Source": "Unknown" } }, { "Name": "TimeBetweenRepetitions", "Value": 12.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } } ] } ], "TimeUnit": "h" }, { "Name": "Muirhead2002_Treatment_Sildenafil_PO_100mg_97h", "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": 100.0, "Unit": "mg" }, { "Name": "Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" } ] } ], "Parameters": [ { "Name": "Start time", "Value": 97.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "NumberOfRepetitions", "Value": 1.0 }, { "Name": "TimeBetweenRepetitions", "Value": 0.0, "Unit": "h" } ] } ], "TimeUnit": "h" }, { "Name": "Muirhead2002_Control_Sildenafil_PO_100mg", "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": 100.0, "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" } ], "Simulations": [ { "Name": "Muirhead2002_Control", "Model": "4Comp", "ObservedData": [ "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "End time", "Value": 2.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h", "ValueOrigin": { "Source": "Unknown" } } ] }, { "Parameters": [ { "Name": "Start time", "Value": 2.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "End time", "Value": 24.0, "Unit": "h" }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|Muirhead2002_Control_Sildenafil_PO_100mg|Sildenafil Tablet|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Sildenafil|Plasma (Peripheral Venous Blood)" ], "OutputMappings": [ { "Scaling": "Log", "Path": "Muirhead2002_Control|Organism|PeripheralVenousBlood|Sildenafil|Plasma (Peripheral Venous Blood)", "ObservedData": "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)" } ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Sildenafil", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "Measurement", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_PERMEABILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Warrington", "MoleculeName": "CYP3A4" }, { "MoleculeName": "AADAC" }, { "MoleculeName": "UGT1A4" }, { "Name": "CYP2C9-Warrington", "MoleculeName": "CYP2C9" }, { "Name": "CYP2C19-Warrington", "MoleculeName": "CYP2C19" } ], "Protocol": { "Name": "Muirhead2002_Control_Sildenafil_PO_100mg", "Formulations": [ { "Name": "Sildenafil Tablet", "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": "Sildenafil-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "Muirhead2002_Control|Organism|PeripheralVenousBlood|Sildenafil|Plasma (Peripheral Venous Blood)", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 3 } }, { "Name": "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)-Sildenafil-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|Time", "Y": "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|ObservedData|Peripheral Venous Blood|Plasma|Sildenafil|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 2, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "Time Profile Analysis", "FontAndSize": { "Fonts": { "AxisSize": 10, "LegendSize": 8, "TitleSize": 16, "DescriptionSize": 12, "OriginSize": 8, "FontFamilyName": "Microsoft Sans Serif", "WatermarkSize": 32 } }, "Settings": { "SideMarginsEnabled": true, "LegendPosition": "None", "BackColor": "#FFFFFF", "DiagramBackColor": "#FFFFFF" }, "OriginText": "Erythromycin-Sildenafil-DDI\nMuirhead2002_Control\n2023-11-28 18:24" } ] }, { "Name": "Muirhead2002_Treatment", "Model": "4Comp", "ObservedData": [ "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)" ], "Solver": {}, "OutputSchema": [ { "Parameters": [ { "Name": "Start time", "Value": 0.0, "Unit": "h" }, { "Name": "End time", "Value": 97.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h", "ValueOrigin": { "Source": "Unknown" } } ] }, { "Parameters": [ { "Name": "Start time", "Value": 97.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "End time", "Value": 99.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "Resolution", "Value": 20.0, "Unit": "pts/h", "ValueOrigin": { "Source": "Unknown" } } ] }, { "Parameters": [ { "Name": "Start time", "Value": 99.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "End time", "Value": 121.0, "Unit": "h", "ValueOrigin": { "Source": "Unknown" } }, { "Name": "Resolution", "Value": 4.0, "Unit": "pts/h" } ] } ], "Parameters": [ { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_10|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_2|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_3|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_4|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_5|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_6|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_7|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_8|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Erythromycin_PO_500mg_BID|Erythromycin_Weibull_filmtablet|Application_9|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Applications|Muirhead2002_Treatment_Sildenafil_PO_100mg_97h|Sildenafil Tablet|Application_1|ProtocolSchemaItem|Volume of water/body weight", "Value": 3.5, "Unit": "ml/kg" }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Caecum_int_Caecum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonAscendens_int_ColonAscendens_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonDescendens_int_ColonDescendens_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonSigmoid_int_ColonSigmoid_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|ColonTransversum_int_ColonTransversum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Duodenum_int_Duodenum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerIleum_int_LowerIleum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|LowerJejunum_int_LowerJejunum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|Rectum_int_Rectum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperIleum_int_UpperIleum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Sildenafil|P (interstitial->intracellular)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Neighborhoods|UpperJejunum_int_UpperJejunum_cell|Sildenafil|P (intracellular->interstitial)", "Value": 0.0017810360334, "Unit": "cm/min", "ValueOrigin": { "Source": "Unknown" } }, { "Path": "Undefined Liver|Reference concentration", "Value": 1.0, "Unit": "µmol/l" }, { "Path": "Undefined Liver|t1/2 (intestine)", "Value": 1380.0, "Unit": "min" }, { "Path": "Undefined Liver|t1/2 (liver)", "Value": 2160.0, "Unit": "min" } ], "OutputSelections": [ "Organism|PeripheralVenousBlood|Erythromycin|Plasma (Peripheral Venous Blood)", "Organism|PeripheralVenousBlood|Sildenafil|Plasma (Peripheral Venous Blood)" ], "OutputMappings": [ { "Scaling": "Log", "Path": "Muirhead2002_Treatment|Organism|PeripheralVenousBlood|Sildenafil|Plasma (Peripheral Venous Blood)", "ObservedData": "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)" } ], "Individual": "European (P-gp modified, CYP3A4 36 h)", "Compounds": [ { "Name": "Erythromycin", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - Charge dependent Schmitt" ], "Alternatives": [ { "AlternativeName": "Erythromycin stearate film-coated tablet", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Fitted", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Biotransformation_fitted", "MoleculeName": "CYP3A4" }, { "MoleculeName": "AADAC" }, { "MoleculeName": "UGT1A4" }, { "MoleculeName": "CYP2C9" }, { "MoleculeName": "CYP2C19" }, { "Name": "Total Hepatic Clearance-fitted", "SystemicProcessType": "Hepatic" }, { "MoleculeName": "P-gp" }, { "Name": "OATP1B1-fitted", "MoleculeName": "OATP1B1" }, { "Name": "Glomerular Filtration-fitted", "SystemicProcessType": "GFR" } ], "Protocol": { "Name": "Muirhead2002_Treatment_Erythromycin_PO_500mg_BID", "Formulations": [ { "Name": "Erythromycin_Weibull_filmtablet", "Key": "Formulation" } ] } }, { "Name": "Sildenafil", "CalculationMethods": [ "Cellular partition coefficient method - Rodgers and Rowland", "Cellular permeability - PK-Sim Standard" ], "Alternatives": [ { "AlternativeName": "Measurement", "GroupName": "COMPOUND_SOLUBILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_PERMEABILITY" }, { "AlternativeName": "Optimized", "GroupName": "COMPOUND_INTESTINAL_PERMEABILITY" } ], "Processes": [ { "Name": "CYP3A4-Warrington", "MoleculeName": "CYP3A4" }, { "MoleculeName": "AADAC" }, { "MoleculeName": "UGT1A4" }, { "Name": "CYP2C9-Warrington", "MoleculeName": "CYP2C9" }, { "Name": "CYP2C19-Warrington", "MoleculeName": "CYP2C19" } ], "Protocol": { "Name": "Muirhead2002_Treatment_Sildenafil_PO_100mg_97h", "Formulations": [ { "Name": "Sildenafil Tablet", "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": "µg/l", "Dimension": "Concentration (molar)", "Type": "Y", "GridLines": false, "Visible": true, "DefaultColor": "#FFFFFF", "DefaultLineStyle": "Solid", "Scaling": "Log", "NumberMode": "Normal" } ], "Curves": [ { "Name": "Erythromycin-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "Muirhead2002_Treatment|Organism|PeripheralVenousBlood|Erythromycin|Plasma (Peripheral Venous Blood)", "CurveOptions": { "Color": "#FF0000", "LegendIndex": 1 } }, { "Name": "Sildenafil-Peripheral Venous Blood-Plasma-Concentration", "X": "Time", "Y": "Muirhead2002_Treatment|Organism|PeripheralVenousBlood|Sildenafil|Plasma (Peripheral Venous Blood)", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 2 } }, { "Name": "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)-Sildenafil-Peripheral Venous Blood-Plasma-ArithmeticMean", "X": "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|Time", "Y": "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|ObservedData|Peripheral Venous Blood|Plasma|Sildenafil|ArithmeticMean", "CurveOptions": { "Color": "#0000FF", "LegendIndex": 3, "LineStyle": "None", "Symbol": "Circle" } } ], "Name": "Time Profile Analysis", "FontAndSize": { "Fonts": { "AxisSize": 10, "LegendSize": 8, "TitleSize": 16, "DescriptionSize": 12, "OriginSize": 8, "FontFamilyName": "Microsoft Sans Serif", "WatermarkSize": 32 } }, "Settings": { "SideMarginsEnabled": true, "LegendPosition": "RightInside", "BackColor": "#00FFFFFF", "DiagramBackColor": "#FFFFFF" }, "OriginText": "Erythromycin-Sildenafil-DDI\nMuirhead2002_Treatment\n2023-11-28 19:47" } ], "Interactions": [ { "Name": "CYP3A4-MBI", "MoleculeName": "CYP3A4", "CompoundName": "Erythromycin" } ] } ], "ObservedData": [ { "Name": "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE", "Type": "String" }, { "Name": "ID", "Value": 16070.0, "Type": "Double" }, { "Name": "Study Id", "Value": "Muirhead 2002a", "Type": "String" }, { "Name": "Reference", "Value": "https://pubmed.ncbi.nlm.nih.gov/11879258/", "Type": "String" }, { "Name": "Source", "Value": "Fig. 1", "Type": "String" }, { "Name": "Grouping", "Value": "Erythromycin DDI, control group, D1", "Type": "String" }, { "Name": "Data type", "Value": "aggregated", "Type": "String" }, { "Name": "N", "Value": 13.0, "Type": "Double" }, { "Name": "Molecule", "Value": "Sildenafil", "Type": "String" }, { "Name": "Species", "Value": "Human", "Type": "String" }, { "Name": "Organ", "Value": "Peripheral Venous Blood", "Type": "String" }, { "Name": "Compartment", "Value": "Plasma", "Type": "String" }, { "Name": "Route", "Value": "PO", "Type": "String" }, { "Name": "Dose", "Value": "100 mg", "Type": "String" }, { "Name": "Times of Administration [h]", "Value": 0.0, "Type": "Double" }, { "Name": "Formulation", "Value": "Tablet", "Type": "String" }, { "Name": "Food state", "Value": "Fed", "Type": "String" }, { "Name": "Comment", "Value": ".", "Type": "String" } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Path": "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|ObservedData|Peripheral Venous Blood|Plasma|Sildenafil|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "MolWeight": 474.58 }, "Values": [ 451.900574, 530.7018, 443.85965, 370.687134, 290.277771, 239.619873, 127.046791, 63.5233955, 55.4824562, 29.7514629, 23.3187141 ], "Dimension": "Concentration (mass)", "Unit": "ng/ml" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Path": "Muirhead 2002a - Erythromycin DDI, control group, D1 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined" }, "Values": [ 0.33, 1.0, 1.25, 2.0, 3.0, 4.0, 6.0, 10.0, 12.0, 18.0, 24.0 ], "Dimension": "Time", "Unit": "h" } }, { "Name": "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)", "ExtendedProperties": [ { "Name": "DB Version", "Value": "OSP DATABASE", "Type": "String" }, { "Name": "ID", "Value": 16073.0, "Type": "Double" }, { "Name": "Study Id", "Value": "Muirhead 2002a", "Type": "String" }, { "Name": "Reference", "Value": "https://pubmed.ncbi.nlm.nih.gov/11879258/", "Type": "String" }, { "Name": "Source", "Value": "Fig. 1", "Type": "String" }, { "Name": "Grouping", "Value": "Erythromycin DDI, treatment group, D6", "Type": "String" }, { "Name": "Data type", "Value": "aggregated", "Type": "String" }, { "Name": "N", "Value": 13.0, "Type": "Double" }, { "Name": "Molecule", "Value": "Sildenafil", "Type": "String" }, { "Name": "Species", "Value": "Human", "Type": "String" }, { "Name": "Organ", "Value": "Peripheral Venous Blood", "Type": "String" }, { "Name": "Compartment", "Value": "Plasma", "Type": "String" }, { "Name": "Route", "Value": "PO", "Type": "String" }, { "Name": "Dose", "Value": "100 mg", "Type": "String" }, { "Name": "Times of Administration [h]", "Value": 120.0, "Type": "Double" }, { "Name": "Formulation", "Value": "Tablet", "Type": "String" }, { "Name": "Food state", "Value": "Fed", "Type": "String" }, { "Name": "Comment", "Value": ".", "Type": "String" } ], "Columns": [ { "Name": "Avg", "QuantityInfo": { "Path": "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|ObservedData|Peripheral Venous Blood|Plasma|Sildenafil|ArithmeticMean" }, "DataInfo": { "Origin": "Observation", "AuxiliaryType": "Undefined", "MolWeight": 474.6 }, "Values": [ 956.8713, 1113.66956, 953.654968, 786.4035, 614.3275, 563.6696, 257.309937, 171.271927, 86.8421, 61.11111, 53.8742676 ], "Dimension": "Concentration (mass)", "Unit": "µg/l" } ], "BaseGrid": { "Name": "Time", "QuantityInfo": { "Path": "Muirhead 2002a - Erythromycin DDI, treatment group, D6 - Sildenafil - PO - 100 mg - Plasma - agg. (n=13)|Time", "Type": "Time" }, "DataInfo": { "Origin": "BaseGrid", "AuxiliaryType": "Undefined" }, "Values": [ 97.333, 97.666, 98.333, 99.0, 100.0, 101.0, 103.0, 107.0, 109.0, 115.0, 121.0 ], "Dimension": "Time", "Unit": "h" } } ] }