MULTISITE KINETIC ANALYSIS OF INTERACTIONS BETWEEN PROTOTYPICAL CYP3A4 SUBGROUP SUBSTRATES: MIDAZOLAM, TESTOSTERONE, AND NIFEDIPINE

• Published in: Drug metabolism and disposition Vol. 31; no. 9; pp. 1108 - 1116
• Main Authors: GALETIN, Aleksandra, CLARKE, Stephen E, HOUSTON, J. Brian
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.09.2003
• Subjects: Binding Sites; Biological and medical sciences; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - metabolism; Drug Interactions; Felodipine - metabolism; General pharmacology; Humans; Kinetics; Medical sciences; Midazolam - metabolism; Models, Biological; Nifedipine - metabolism; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Substrate Specificity; Testosterone - metabolism; Tumor Cells, Cultured; Human; Drug combination; Androgen; Isozyme; Cytochrome P450; Calcium antagonist; Metabolism; In vitro; Nifedipine; Substrate; Testosterone; Benzodiazepine derivatives; Dihydropyridine derivatives; Drug interaction; Midazolam; Sex steroid hormone; Pharmacokinetics; Felodipine

The potential of substrates and modifiers of CYP3A4 to show differential effects, attributed to the existence of multiple binding sites, confounds the straightforward prediction of in vivo drug-drug interactions from in vitro data. A set of in vitro interaction studies was performed in human lymphob...