The impact of genetic polymorphisms on the pharmacokinetics of efavirenz in African children.

ABSTRACT:

Aims

Using a model-based approach, the efavirenz steady-state pharmacokinetics in African children is characterized, quantifying demographic and genotypic effects on the drug's disposition. Simulations are also conducted allowing prediction of optimized doses of efavirenz in this population.

Methods

We modelled the steady-state population pharmacokinetics of efavirenz in Ugandan and Zambian children using nonlinear mixed-effects modelling. Individual mid-dose efavirenz concentrations were derived and simulations explored genotype-based dose optimization strategies.

Results

A two-compartment model with absorption through transit compartments well described 2086 concentration-time points in 169 children. The combined effect of single nucleotide polymorphisms (SNPs) 516G

SUBMITTER: Bienczak A 

PROVIDER: S-EPMC4917805 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature