Content area
Abstract
To study the pharmacokinetic characteristics of voriconazole in healthy Chinese male volunteers in relation to cytochrome P450 (CYP) 2C19 genotype status, including ultra-rapid metabolizers (URMs), homozygous extensive metabolizers (EMs), and poor metabolizers (PMs).
Twenty healthy Chinese male volunteers were recruited for the study. Of these, four were CYP2C19 heterozygous URMs (*1/*17), eight were CYP2C19 homozygous EMs (*1/*1), and eight were CYP2C19 PMs (*2/*2). After a single oral dose of 200 mg voriconazole, plasma concentrations of voriconazole were determined for a 24-h period by liquid chromatography-mass spectrometry/mass spectrometry.
In Chinese male subjects, the allele frequencies of the CYP2C19*17 and CYP2C19*2 alleles were 0.64 and 35.6%, respectively, and both alleles were in Hardy-Weinberg equilibrium. The area under the concentration-time curve (AUC) from predose to 24 h (AUC0-24) and from predose to infinity (AUC0-∞), and apparent oral clearance (CL/F) of voriconazole were statistically different among all three genotypic groups (P<0.001, respectively). The maximum plasma concentration (Cmax) value of URMs also showed statistically significant differences from those of EMs and PMs (P=0.036 and P =0.035, respectively). The elimination half-life (t½) in URMs was 87% (P=0.58) of that in EMs and 51% (P=0.002) of that in PMs.
Our data indicate that the presence of the CYP2C19*17 allele results in ultra-rapid metabolism of voriconazole after a single oral dose. [PUBLICATION ABSTRACT]