CYP2B6 polymorphism and nonnucleoside reverse transcriptase inhibitor plasma concentrations in Chinese HIV-infected patients

Ther Drug Monit. 2010 Oct;32(5):573-8. doi: 10.1097/FTD.0b013e3181ea953c.

Abstract

The purpose of this study was to investigate the frequency of CYP2B6 polymorphisms and their influence on plasma concentrations of efavirenz and nevirapine in HIV-infected Chinese patients. After written informed consent, 159 patients were enrolled at Shanghai Public Health Clinical Center. Genotyping for 516 G>T, 785 A>G, 983 T>C, and 1459 T>C polymorphisms in CYP2B6, together with CYP3A4 -392 A>G, CYP3A5 6986 A>G, and ABCB1 (2677 G>T/A, 3435 C>T), were performed. Plasma efavirenz and nevirapine concentrations of 120 patients at steady state were assessed by high-performance liquid chromatography-mass spectrometry. The minor allele frequency for CYP2B6 516 G>T, 785 A>G, 983 T>C, and 1459 T>C was 0.16, 0.24, 0, and 0, respectively; and 0.07, 0.32, 0.15, and 0.35 for CYP3A4 -392 A>G, CYP3A5 6986 A>G, ABCB1 2677 G>T/A, and ABCB1 3435 C>T, respectively. Univariate analysis indicated associations between 516 G>T (P < 0.01) with efavirenz but not nevirapine plasma concentrations. None of other genetic variants was associated with plasma efavirenz or nevirapine concentrations. Although CYP2B6 516 G>T was associated with high plasma efavirenz concentrations, such an association was not evident with nevirapine in this Chinese patient population. CYP3A4 -392 A>G, CYP3A5 6986 A>G, and ABCB1 (2677 G>T/A, 3435 C>T) had no significant impact on plasma efavirenz or nevirapine concentrations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • Adult
  • Aged
  • Alkynes
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Asian Continental Ancestry Group*
  • Benzoxazines / blood*
  • Benzoxazines / pharmacokinetics
  • Benzoxazines / therapeutic use
  • China
  • Chromatography, High Pressure Liquid
  • Cyclopropanes
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A / genetics
  • Female
  • Gene Frequency
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / enzymology
  • Humans
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Nevirapine / blood*
  • Nevirapine / pharmacokinetics
  • Nevirapine / therapeutic use
  • Oxidoreductases, N-Demethylating / genetics*
  • Polymorphism, Genetic*
  • Reverse Transcriptase Inhibitors / blood
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Reverse Transcriptase Inhibitors / therapeutic use

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • Aryl Hydrocarbon Hydroxylases
  • CYP2B6 protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Oxidoreductases, N-Demethylating
  • efavirenz