Comparison of enzyme kinetic parameters obtained in vitro for reactions mediated by human CYP2C enzymes including major CYP2C9 variants.
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.
Rokitta
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Department of Pharmacology, University of Cologne, Gleueler Str. 24, 50931 Cologne, Germany. dennis.rokitta@uni-koeln.de
Fuhr
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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
D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D064417:Vitamin K Epoxide Reductases