Probenecid and zidovudine metabolism

Lancet. 1989 Aug 26;2(8661):473-5. doi: 10.1016/s0140-6736(89)92087-4.


The effects of probenecid, a known inhibitor of glucuronidation, on the pharmacokinetics of zidovudine were assessed in eight subjects receiving zidovudine as treatment for human immunodeficiency virus infection. Zidovudine plasma concentrations were measured while subjects were receiving zidovudine alone, after 3 days of zidovudine plus 500 mg probenecid every 8 h, and after 3 days of zidovudine plus 500 mg probenecid plus 260 mg quinine sulphate every 8 h. A median increase of 80% in the area under the zidovudine plasma concentration/time curve occurred with the addition of probenecid. Quinine sulphate prevented the probenecid effect but had no effect on zidovudine kinetics when taken without probenecid by four other subjects. All of the effects were secondary to changes in zidovudine metabolism, since neither probenecid nor quinine changed the renal elimination of zidovudine. Probenecid could be used in combination with zidovudine to extend the interval between doses and reduce the daily requirement for zidovudine, thus enhancing convenience and reducing costs.

Publication types

  • Clinical Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Related Complex / drug therapy
  • AIDS-Related Complex / metabolism
  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / metabolism*
  • Administration, Oral
  • Adult
  • Aged
  • Chromatography, High Pressure Liquid
  • Clinical Trials as Topic
  • Drug Administration Schedule
  • Drug Evaluation
  • Drug Interactions
  • Drug Therapy, Combination
  • Humans
  • Male
  • Middle Aged
  • Patient Compliance
  • Probenecid / administration & dosage
  • Probenecid / pharmacology*
  • Quinine / administration & dosage
  • Quinine / pharmacology*
  • Zidovudine / administration & dosage
  • Zidovudine / metabolism*
  • Zidovudine / therapeutic use


  • Zidovudine
  • Quinine
  • Probenecid