title: CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans.
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.
  
  
  CONCLUSIONS
  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.
authors: Laboratory for International Alliance, RIKEN Center for Genomic Medicine, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
authors: Milimo
authors: M
authors: Maimbo
authors: Kazuma
authors: K
authors: Kiyotani
authors: Taisei
authors: T
authors: Mushiroda
authors: Collen
authors: C
authors: Masimirembwa
authors: Yusuke
authors: Y
authors: Nakamura
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D048588:Benzoxazines / Q000097:blood* / Q000493:pharmacokinetics; D003521:Cyclopropanes; D065702:Cytochrome P-450 CYP2B6; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018894:Reverse Transcriptase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics; D015030:Zimbabwe
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating; C098320:efavirenz