Differential genotype dependent inhibition of CYP2C9 in humans.

ABSTRACT: The effects of genetic polymorphisms in drug-metabolizing enzymes (e.g., CYP2C9(*)3) on drug clearance have been well characterized but much less is known about whether these polymorphisms alter susceptibility to drug-drug interactions. Previous in vitro work has demonstrated that genotype-dependent inhibition of CYP2C9 mediated flurbiprofen metabolism, suggesting the possibility of genotype-dependent inhibition interactions in vivo. In the current study, flurbiprofen was used as a probe substrate and fluconazole as a prototypical inhibitor to investigate whether genotype-dependent inhibition of CYP2C9 occurs in vivo. From 189 healthy volunteers who were genotyped for CYP2C9 polymorphisms, 11 control subjects (CYP2C9(*)1/(*)1), 9 heterozygous and 2 homozygous for the CYP2C9(*)3 allele part

SUBMITTER: Kumar V 

PROVIDER: S-EPMC2435413 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature