CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population
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Date
2016
Journal Title
Journal ISSN
Volume Title
Publisher
Future Medicine Ltd: Pharmacogenomics
Abstract
To assess genotype effect on efavirenz (EFV) pharmacokinetics, treatment
outcomes and provide genotype-based EFV doses recommendations during for
tuberculosis (TB)-HIV-1 cotreatment. Materials & methods: EFV concentrations
from 158 HIV-TB co-infected patients treated with EFV/lamivudine/zidovidine and
rifampicin were analyzed. Genotype and CD4 and viral load data were analyzed using
a population PK model. Results: Simulated AUCs for 600 mg EFV dose were 1.2- and
2.4-times greater than the product label for Ugandans in general and CYP2B6*6/*6
genotypes respectively. EFV daily doses of 450 and 250 mg for Ugandans and
CYP2B6*6/*6 genotypes, respectively, yielded simulated exposures comparable to
the product label. Conclusions: Around 450 and 250 mg daily doses might meet EFV
dosing needs of HIV-TB infected Ugandans in general and CYP2B6*6/*6 genotypes,
respectively.
Description
Keywords
African population, Cotreatment, Dose recommendations, HIV-TB, Efavirenz
Citation
Mukonzo, J. K., Bisaso, R. K., Ogwal-Okeng, J., Gustafsson, L. L., Owen, J. S., & Aklillu, E. (2016). CYP2B6 genotype-based efavirenz dose recommendations during rifampicin-based antituberculosis cotreatment for a sub-Saharan Africa population. Pharmacogenomics, 17(6), 603-613.