A novel polymorphism in ABCB1 gene, CYP2B6*6 and sex predict single-dose efavirenz population pharmacokinetics in Ugandans.

ABSTRACT:

Aims

Efavirenz exhibits pharmacokinetic variability causing varied clinical response. The aim was to develop an integrated population pharmacokinetic/pharmacogenetic model and investigate the impact of genetic variations, sex, demographic and biochemical variables on single-dose efavirenz pharmacokinetics among Ugandan subjects, using NONMEM.

Methods

Efavirenz plasma concentrations (n = 402) from 121 healthy subjects were quantified by high-performance liquid chromatography. Subjects were genotyped for 30 single nucleotide polymorphisms (SNPs), of which six were novel SNPs in CYP2B6, CYP3A5 and ABCB1. The efavirenz pharmacokinetics was described by a two-compartment model with zero- followed by first-order absorption.

Results

Apparent oral clearance (95% confidence in

SUBMITTER: Mukonzo JK 

PROVIDER: S-EPMC2791975 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature