title: Comparison of enzyme kinetic parameters obtained in vitro for reactions mediated by human CYP2C enzymes including major CYP2C9 variants.
abstract: Cytochrome P450 (CYP) 2C enzymes contribute to the metabolism of about 30% of all drugs. Known polymorphisms of the respective enzymes and drug-drug interactions have a major impact on the efficacy and safety of some CYP2C substrate drugs. In vivo - in vitro correlations including prediction of the effect of such covariates requires quantitative information on enzyme kinetics. In this article there will be a summary of the values of the Michaelis-Menten constant (K(m)), the maximal velocity (V(max)) and the intrinsic clearance (Cl(int); V(max)/K(m)) for 84 substrates (100 reactions) reported to be mediated by CYP2C9 (variant enzymes CYP2C9.1, CYP2C9.2 and CYP2C9.3), CYP2C8 and/or CYP2C19. Particularly contradictory findings for the same reactions call for some standardization in the assessment of enzyme kinetics.
authors.affiliation: Department of Pharmacology, University of Cologne, Gleueler Str. 24, 50931 Cologne, Germany. dennis.rokitta@uni-koeln.de
authors.forename: D
authors.initials: D
authors.lastname: Rokitta
authors.forename: U
authors.initials: U
authors.lastname: Fuhr
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000493:pharmacokinetics* / Q000592:standards; D065729:Cytochrome P-450 CYP2C9; D004347:Drug Interactions / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000493:pharmacokinetics* / Q000592:standards; D011110:Polymorphism, Genetic; D013379:Substrate Specificity / Q000235:genetics; D064417:Vitamin K Epoxide Reductases
chemical_list: D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D064417:Vitamin K Epoxide Reductases