Abstract

OBJECTIVES:

The aim of the study was to characterize the impact of the cytochrome P450 2B6 (CYP2B6), CYP3A4, CYP3A5 and ATP-binding cassette sub-family B member 1 (ABCB1) polymorphisms on nevirapine plasma concentrations.

METHODS:

A total of 104 patients (82% male; 26% non-Caucasian) were genotyped for eight single nucleotide polymorphisms at four loci (CYP2B6, CYP3A4, CYP3A5 and MDR1). Nevirapine plasma concentrations were determined using high-performance liquid chromatography.

RESULTS:

Non-Caucasian ethnicity [5609 ng/mL (n=27) for non-Caucasians vs. 3771 ng/mL (n=77) for Caucasians; P<0.0001] and CYP2B6 516G-->T [GG, 3574 ng/mL (n=50); GT, 4634 ng/mL (n=50); TT, 8170 ng/mL (n=4); P(analysis of variance (anova))=0.001] were significantly associated with a higher nevirapine trough concentration (C(trough)). The latter association was maintained with both 200 mg twice daily (bid) and 400 mg once daily (qd) dosing [GG, 3527 ng/mL (n=30); GT, 4525 ng/mL (n=32); TT, 7020 ng/mL (n=2); P(anova)=0.05 and GG, 3645 ng/mL (n=20); GT, 4861 ng/mL (n=17); TT, 9508 ng/mL (n=2); P(anova)=0.01, respectively]. In a multivariable analysis, CYP2B6 516G-->T and non-Caucasian ethnicity remained significant predictors of nevirapine C(trough) but CYP2B6 516G-->T homozygosity had the greatest effect (108% higher, 46% higher). No associations were found between nevirapine C(trough) and the remaining polymorphisms.

CONCLUSION:

In this population, both non-Caucasian ethnicity and carriage of the variant allele of CYP2B6 516G-->T were significant predictors of nevirapine C(trough). The association between CYP2B6 516G-->T and higher plasma nevirapine exposure was maintained at both bid and qd dosing.