A Semiphysiological Population Pharmacokinetic Model for Dynamic Inhibition of Liver and Gut Wall Cytochrome P450 3A by Voriconazole

• Published in: Clinical pharmacokinetics Vol. 52; no. 9; pp. 763 - 781
• Main Authors: Frechen, Sebastian, Junge, Lisa, Saari, Teijo I., Suleiman, Ahmed Abbas, Rokitta, Dennis, Neuvonen, Pertti J., Olkkola, Klaus T., Fuhr, Uwe
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2013; Adis International; Springer Nature B.V
• Subjects: Antifungal Agents - administration & dosage; Antifungal Agents - blood; Antifungal Agents - pharmacokinetics; Biological and medical sciences; Cross-Over Studies; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; General pharmacology; Humans; Internal Medicine; Liver - enzymology; Male; Medical sciences; Medicine; Medicine & Public Health; Midazolam - administration & dosage; Midazolam - blood; Midazolam - pharmacokinetics; Models, Biological; Original Research Article; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacotherapy; Pyrimidines - administration & dosage; Pyrimidines - blood; Pyrimidines - pharmacokinetics; Triazoles - administration & dosage; Triazoles - blood; Triazoles - pharmacokinetics; Voriconazole; Objective Function Value; CYP3A Activity; Midazolam; Visual Predictive Check; Voriconazole; Human; Population pharmacokinetics; Wall; Digestive system; Enzyme; Isozyme; Azole derivatives; Cytochrome P450; Liver; Gut; Antifungal agent; Triazole derivatives; Inhibitor; Dynamic model

Background Accurate predictions of cytochrome P450 (CYP) 3A-mediated drug-drug interactions (DDIs) account for dynamic changes of CYP3A activity at both major expression sites (liver and gut wall) by considering the full pharmacokinetic profile of the perpetrator and the substrate. Physiological-bas...