Received for publication December 10, 2007.
Revised May 15, 2008.
Accepted for publication May 16, 2008.

The Influence of CYP3A5 Genotype on Dexamethasone Induction of CYP3A Activity in African Americans

Abstract

The CYP3A5*1 allele has been associated with differences in the metabolism of some CYP3A substrates. CYP3A polymorphism may also influence susceptibility for certain drug interactions. We have previously noted a correlation between basal CYP3A activity and the inductive effects of dexamethasone using the erythromycin breath test (ERBT). To determine if CYP3A5 polymorphism influences induction of CYP3A activity, we examined the effect of an anti-emetic regimen of dexamethasone, and the prototypical inducer rifampin, on the ERBT in a African American volunteers prospectively stratified by CYP3A5*1 allele carrier-status. Mean basal ERBTs were significantly higher in CYP3A5*1 carriers (2.71% ± 0.53%) versus non-carriers (2.12% ± 0.37%, P = 0.006). Rifampin increased ERBTs in CYP3A5*1 carriers (4.68% vs 2.60%, P = 0.0008) and non-carriers (3.55% vs 2.11%, P = 0.0017), while dexamethasone increased ERBTs only in CYP3A5*1 non-carriers (3.03% vs 2.14%, P = 0.031). CYP3A5 polymorphism appears to influence susceptibility to induction-type drug interactions for some inducers, and CYP3A5*1 non-carriers may be more susceptible to the inductive effects of dexamethasone due to lower basal CYP3A activity.

Key words: CYP induction, CYP3A, cytochrome P450, drug interactions, genotype, induction