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Eur J Clin Pharmacol. 2012 Mar;68(3):267-71. doi: 10.1007/s00228-011-1118-0. Epub 2011 Sep 8.

CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans.

Author information

1
Laboratory for International Alliance, RIKEN Center for Genomic Medicine, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.

Abstract

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.

PMID:
21901344
DOI:
10.1007/s00228-011-1118-0
[Indexed for MEDLINE]

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