The effect of probenecid on the pharmacokinetics of zalcitabine in HIV-positive patients

Pharm Res. 1996 Mar;13(3):449-52. doi: 10.1023/a:1016009029536.


Purpose: The purpose of this study was to determine the potential effect of probenecid on the pharmacokinetics of zalcitabine in HIV-positive patients.

Methods: Twelve patients received single oral 1.5 mg doses of zalcitabine alone and during probenecid treatment (500 mg at 8 and 2 hours before and 4 hours after zalcitabine dosing) in an open-label, randomized two-way crossover study with a one-week washout period between treatments. Serial blood and urine samples were collected over a 24 hour period and assayed for zalcitabine by a modified GC/MS method.

Results: Coadministration of probenecid with zalcitabine resulted in a decrease in mean (%CV) renal clearance of zalcitabine from 310 (28%) ml/min when zalcitabine was given alone to 180 (22%) ml/min with probenecid and a prolonged half-life from 1.7 hours to 2.5 hours. Mean AUCs increased from 59 ng.h/ml when zalcitabine was given alone to 91 ng.h/ml when given with probenecid. Considering the short half-life of zalcitabine (1-3 hours) relative to its dosing schedule, the pharmacokinetic changes observed in this study are not expected to result in significant accumulation during chronic dosing.

Conclusions: The results of this study show that co-administration of probenecid with zalcitabine results in a moderate decrease in renal clearance of zalcitabine due to inhibition of renal tubular secretion and a 50% increase in drug exposure. Although well tolerated in this single-dose study, patients taking this combination should be monitored closely for signs of toxicity and dosage reduction should be considered if warranted.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / urine
  • Cross-Over Studies
  • Drug Administration Schedule
  • Drug Interactions
  • Female
  • HIV Seropositivity / drug therapy*
  • HIV Seropositivity / metabolism*
  • Half-Life
  • Humans
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism
  • Male
  • Middle Aged
  • Probenecid / pharmacology*
  • Uricosuric Agents / pharmacokinetics*
  • Zalcitabine / blood
  • Zalcitabine / pharmacokinetics*
  • Zalcitabine / urine


  • Antiviral Agents
  • Uricosuric Agents
  • Zalcitabine
  • Probenecid