Genetics of Nevirapine Metabolic Pathways at Steady State in HIV-Infected Cambodians

Antimicrob Agents Chemother. 2017 Nov 22;61(12):e00733-17. doi: 10.1128/AAC.00733-17. Print 2017 Dec.

Abstract

Nevirapine is metabolized by several hepatic cytochrome P450 (CYP) isoforms to generate four primary hydroxylated metabolites: 2-hydroxynevirapine, 3-hydroxynevirapine, 8-hydroxynevirapine, and 12-hydroxynevirapine. The present study characterized associations between genetic polymorphisms and metabolite ratios in HIV-infected Cambodians. We demonstrate associations between CYP2B6 polymorphisms and metabolite ratios for both 3-hydroxynevirapine and 8-hydroxynevirapine, suggesting involvement of CYP2B6 in generating these metabolites.

Keywords: genetic polymorphisms; metabolism pathways; nevirapine; population pharmacokinetics.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Asian People / genetics
  • Cambodia
  • Cytochrome P-450 CYP2B6 / genetics*
  • Female
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Nevirapine* / metabolism
  • Nevirapine* / pharmacokinetics
  • Nevirapine* / therapeutic use
  • Polymorphism, Single Nucleotide / genetics

Substances

  • Anti-HIV Agents
  • Nevirapine
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6