Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus

Clin Pharmacol Ther. 1992 Nov;52(5):464-70. doi: 10.1038/clpt.1992.173.

Abstract

Objective: To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine.

Methods: This was designed as a randomized, two-period, two-treatment, crossover study. The patients were 12 men infected with human immunodeficiency virus who had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. On two separate occasions 14 days apart, patients received either zidovudine alone (200 mg every 4 hours while awake) or zidovudine (200 mg every 4 hours while awake) and naproxen (500 mg every 12 hours for 4 days). On the morning of the fifth day, each patient received the final dose of each regimen and blood and urine were serially collected for 8 hours. Pharmacokinetic parameters (area under the serum concentration-time curve [AUC], maximum plasma concentration, terminal half-life, renal clearance, and urinary recovery) were assessed for zidovudine and its glucuronide metabolite.

Main results: Naproxen had no significant effect (< 10% difference between treatment means, p > 0.15, ANOVA) on the above pharmacokinetic parameters for both zidovudine and its metabolite. Although the power of the study to detect these small differences was < 80% at the 5% significance level, differences ranging from 12.6% for AUC to 38.8% for urinary recovery could be detected with 80% power.

Conclusion: Therapeutic doses of naproxen do not significantly affect the pharmacokinetic disposition of zidovudine.

Publication types

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

MeSH terms

  • Adult
  • Analysis of Variance
  • Chromatography, High Pressure Liquid
  • Drug Interactions
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Naproxen / pharmacology*
  • Radioimmunoassay
  • Zidovudine / pharmacokinetics*
  • Zidovudine / therapeutic use

Substances

  • Zidovudine
  • Naproxen