Dissimilarities in the metabolism of antiretroviral drugs used in HIV pre-exposure prophylaxis in colon and vagina tissues

Biochem Pharmacol. 2013 Oct 1;86(7):979-90. doi: 10.1016/j.bcp.2013.08.013. Epub 2013 Aug 18.


Attempts to prevent HIV infection through pre-exposure prophylaxis (PrEP) include topical application of anti-HIV drugs to the mucosal sites of infection; however, a potential role for local drug metabolizing enzymes in modulating the exposure of the mucosal tissues to these drugs has yet to be explored. Here we present the first report that enzymes belonging to the cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) families of drug metabolizing enzymes are expressed and active in vaginal and colorectal tissue using biopsies collected from healthy volunteers. In doing so, we discovered that dapivirine and maraviroc, a non-nucleoside reverse transcriptase inhibitor and an entry inhibitor currently in development as microbicides for HIV PrEP, are differentially metabolized in colorectal tissue and vaginal tissue. Taken together, these data should help to guide the optimization of small molecules being developed for HIV PrEP.

Keywords: CYP; Colorectal; HIV drug metabolism; Vaginal.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / metabolism*
  • Anti-HIV Agents / pharmacokinetics
  • Chemoprevention / methods
  • Colon / metabolism*
  • Cyclohexanes / metabolism*
  • Cyclohexanes / pharmacokinetics
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • HIV Infections / prevention & control
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Male
  • Maraviroc
  • Mucous Membrane / metabolism
  • Organ Specificity
  • Pyrimidines / metabolism*
  • Pyrimidines / pharmacokinetics
  • Triazoles / metabolism*
  • Triazoles / pharmacokinetics
  • Vagina / metabolism*
  • Young Adult


  • Anti-HIV Agents
  • Cyclohexanes
  • Isoenzymes
  • Pyrimidines
  • Triazoles
  • Cytochrome P-450 Enzyme System
  • Glucuronosyltransferase
  • Maraviroc
  • Dapivirine