Pharmacogenomics of the triazole antifungal agent voriconazole

Abstract

Genetic polymorphisms in drug-metabolizing enzymes are frequently responsible for high variability in the pharmacokinetics of certain drugs leading to large variations in drug efficacy and adverse drug effects, or large ranges of the doses required for optimal drug efficacy. Voriconazole is a triazole antifungal agent which has been available for several years and has potent in vitro and in vivo activity against a broad spectrum of medically important pathogens, including Aspergillus, Cryptococcus and Candida. Voriconazole is extensively metabolized by the cytochrome P450 system with CYP2C19 being the major route for elimination. Thus, polymorphisms in the CYP2C19 gene have substantial impact on the pharmacokinetics of voriconazole and its interactions with other drugs. This article summarizes the current knowledge regarding CYP2C19 and discusses the influences of other drug-metabolizing enzymes and drug transporters on voriconazole disposition.