The effect of cimetidine and ranitidine administration with zidovudine

Pharmacotherapy. Nov-Dec 1995;15(6):701-8.

Abstract

Study objective: To evaluate the possibility of a drug interaction with zidovudine and histamine2-receptor antagonists in individuals infected with the human immunodeficiency virus.

Design: Randomized crossover study.

Setting: University-affiliated research center.

Patients: Six HIV-infected individuals.

Interventions: The subjects received 7-day regimens of zidovudine 600 mg/day alone, zidovudine with cimetidine 1200 mg/day, and zidovudine with ranitidine 300 mg/day.

Measurements and main results: The renal clearance of zidovudine when given alone was 0.41 L/kg/hour, and was reduced to 0.18 L/kg/hour (p = 0.002) when given with cimetidine. In the presence of cimetidine the urinary excretion of zidovudine decreased from 89.5 to 53.7 microM (p = 0.01), the urinary ratio of metabolite to parent increased from 5.16 to 9.96 (p = 0.0001), and the fraction of zidovudine converted to metabolite increased from 0.86 to 0.92 (p = 0.0025).

Conclusion: Cimetidine presumably inhibits the renal clearance of zidovudine by competing for tubular secretion. Based on the observation that neither cimetidine nor ranitidine had a significant effect on serum concentrations of zidovudine or zidovudine glucuronide, a change in the dosage of zidovudine is not warranted.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Anti-Ulcer Agents / administration & dosage
  • Anti-Ulcer Agents / pharmacology*
  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / therapeutic use
  • CD4 Lymphocyte Count / drug effects*
  • CD4-CD8 Ratio / drug effects
  • Cimetidine / administration & dosage
  • Cimetidine / pharmacology*
  • Cross-Over Studies
  • Drug Interactions
  • HIV Infections / drug therapy
  • HIV Infections / metabolism
  • Histamine H2 Antagonists / administration & dosage
  • Histamine H2 Antagonists / pharmacology*
  • Hospitals, University
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Ranitidine / administration & dosage
  • Ranitidine / pharmacology*
  • Zidovudine / analogs & derivatives
  • Zidovudine / blood
  • Zidovudine / pharmacokinetics*
  • Zidovudine / therapeutic use

Substances

  • Anti-Ulcer Agents
  • Antiviral Agents
  • Histamine H2 Antagonists
  • Zidovudine
  • Cimetidine
  • Ranitidine
  • 3'-azido-3'-deoxy-5'-O-beta-glucopyranuronosylthymidine