Effect of diurnal variation, CYP2B6 genotype and age on the pharmacokinetics of nevirapine in African children.

ABSTRACT:

Objectives

To characterize the effects of CYP2B6 polymorphisms, diurnal variation and demographic factors on nevirapine pharmacokinetics in African children.

Methods

Non-linear mixed-effects modelling conducted in NONMEM 7.3 described nevirapine plasma concentration-time data from 414 children aged 0.3-15 years.

Results

Nevirapine pharmacokinetics was best described using a one-compartment disposition model with elimination through a well-stirred liver model accounting for a first-pass effect and transit-compartment absorption. Intrinsic clearance was affected by diurnal variation (characterized using a cosine function with peak amplitude 29% at 12 noon) and CYP2B6 metabolizer status [extensive metabolizer (EM) 516GG|983TT, reference; intermediate metabolizer (IM) 516

SUBMITTER: Bienczak A 

PROVIDER: S-EPMC5161049 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature