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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans
European Journal of Clinical Pharmacology, Volume 68, No. 3, Year 2012
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Description
Objective: Efavirenz, an antiretroviral medicine, is extensively metabolized by cytochrome P450 2B6 (CYP2B6), UDP-glucuronosyltransferase 2B7 (UGT2B7), and CYP2A6. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in these genes with plasma efavirenz levels in Zimbabwean human immunodeficiency virus (HIV)-positive patients treated with efavirenz. Methods: The exon regions of the CYP2B6, CYP2A6, and UGT2B7 genes were re-sequenced in 49 HIV-infected Zimbabwean patients treated with a combination therapy including efavirenz. Associations of SNPs in these three genes with efavirenz plasma concentrations 11-16 h after the administration of treatment were evaluated. Results: Eight patients carrying CYP2B6*6/ *18 showed the highest plasma efavirenz levels, with a fourfold higher concentration than patients who carried CYP2B6*1/*1. Patients with CYP2B6*6/*6 also showed higher efavirenz plasma concentrations than those with CYP2B6*1/*1. Among the 17 and 12 SNPs identified in CYP2A6 and UGT2B7, respectively, no SNP showed a significant association with the plasma efavirenz concentration. Conclusion: Although based on only a limited number of subjects, our results suggest that the CYP2B6*6 and CYP2B6*18 alleles should affect hepatic metabolic activity and elevate the systemic circulation level of efavirenz, which may lead to toxicity in Zimbabwean HIV patients. © 2011 Springer-Verlag.
Authors & Co-Authors
Maimbo, Milimo
Japan, Wako
Riken
Zimbabwe, Harare
African Institute of Biomedical Science and Technology Aibst
Kiyotani, Kazuma
Japan, Wako
Riken
Mushiroda, Taisei
Japan, Wako
Riken
Masimirembwa, Collen Mutowembwa
Zimbabwe, Harare
African Institute of Biomedical Science and Technology Aibst
Nakamura, Yusuke
Japan, Wako
Riken
Japan, Tokyo
The University of Tokyo
Statistics
Citations: 52
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1007/s00228-011-1118-0
e-ISSN:
14321041
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Noncommunicable Diseases