Probenecid Inhibits the Metabolic and Renal Clearances of Zidovudine (AZT) in Human Volunteers

Mohsen A. Hedaya, William F. Elmquist, Ronald J. Sawchuk

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69 Scopus citations


The effect of probenecid on the disposition of AZT was investigated in a pilot study in two healthy volunteers. The pharmacokinetics of AZT were examined after a single oral dose of 200 mg with and without probenecid coadministration in a balanced crossover study. Administration of 500 mg probenecid every 6 hr prior to and during AZT dosing resulted in an increase in the average AUCAZT from 89 µg · min/ml (control) to 191 µg · min/ml during probenecid treatment. This was manifested by a corresponding decrease in CLTOT/F, which is attributed to the inhibitory effect of probenecid on the glucuronidation and renal excretion of AZT. Average CLR and CLTOT/F of AZT decreased from 4.76 and 28.7 to 2.98 and 14.1 ml/min/kg during control and probenecid treatment, respectively. AZT glucuronidation was affected to a greater extent than its renal excretion, as reflected by the decreased ratio of GAZT/AZT urinary recoveries. The terminal half-life of AZT was slightly longer during probenecid administration. That only a small change in the half-life occurred indicates that probenecid also reduced the volume of distribution of AZT. The CLR of GAZT decreased from an average of 11.3 ml/min/kg (control) to 2.63 ml/min/kg during probenecid treatment, resulting in a greater than 3.5-fold increase in AUCGAZT. Probenecid did not affect the blood/plasma distribution or the plasma protein binding of AZT. These preliminary findings suggest that it may be possible to maintain effective plasma AZT concentrations in AIDS patients receiving a reduced daily dose, in combination with probenecid.

Original languageEnglish (US)
Pages (from-to)411-417
Number of pages7
JournalPharmaceutical Research: An Official Journal of the American Association of Pharmaceutical Scientists
Issue number4
StatePublished - Apr 1990


  • AIDS therapy
  • pharmacokinetics
  • probenecid
  • zidovudine


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