Impact of genetic polymorphisms in CYP2C9 and CYP2C19 on the pharmacokinetics of clinically used drugs.

Human cytochrome P450 (CYP) is a superfamily of hemoproteins which oxidize a number of endogenous compounds and xenobiotics. The human CYP2C subfamily consists of four members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. CYP2C9 and CYP2C19 are important drug-metabolizing enzymes and together metabolize approximately 20% of therapeutically used drugs. Forty-two allelic variants for CYP2C9 and 34 for CYP2C19 have been reported. The frequencies of these variants show marked inter-ethnic variation. The functional consequences of genetic polymorphisms have been examined, and many studies have shown the clinical importance of these polymorphisms. Current evidence suggests that taking the genetically determined metabolic capacity of CYP2C9 and CYP2C19 into account has the potential to improve individual risk/benefit relationships. However, more prospective studies with clinical endpoints are needed before the paradigm of "personalized medicine" based on the variants can be established. This review summarizes the currently available important information on this topic.