Pharmacokinetic interaction between ketoconazole and amprenavir after single doses in healthy men

Pharmacotherapy. 1999 Dec;19(12):1378-84. doi: 10.1592/phco.19.18.1378.30905.


Study objective: To determine the effects of coadministration of amprenavir and ketoconazole on the pharmacokinetics of both drugs, and to assess the utility of the erythromycin breath test (ERMBT) to predict and explain these effects.

Design: Open-label, randomized, balanced, single-dose, three-period crossover study.

Setting: University research center.

Subjects: Twelve healthy men.

Intervention: Subjects received amprenavir 1200 mg, ketoconazole 400 mg, and amprenavir 1200 mg plus ketoconazole 400 mg. Each treatment was separated by 14 days.

Measurements and main results: Serial plasma samples for amprenavir and ketoconazole concentrations were measured by high-performance liquid chromatography. Coadministration of the drugs increased amprenavir area under the curve extrapolated to infinity (AUCinfinity) by 31% and reduced its maximum concentration (Cmax) by 16%. Amprenavir increased the AUCinfinity of ketoconazole by 44% and increased the drug's half-life and Cmax by 23% and 19%, respectively. Both agents resulted in substantial inhibition of ERMBT.

Conclusion: Coadministration of ketoconazole and amprenavir results in a statistically significant increase in AUC for both agents, but the changes are not likely to be clinically important.

Publication types

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

MeSH terms

  • Adult
  • Antifungal Agents / blood
  • Antifungal Agents / pharmacokinetics*
  • Breath Tests
  • Carbamates
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Erythromycin / analysis
  • Furans
  • HIV Protease Inhibitors / adverse effects
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / pharmacokinetics*
  • Humans
  • Ketoconazole / adverse effects
  • Ketoconazole / blood
  • Ketoconazole / pharmacokinetics*
  • Male
  • Mixed Function Oxygenases / metabolism
  • Sulfonamides / adverse effects
  • Sulfonamides / blood
  • Sulfonamides / pharmacokinetics*
  • Time Factors


  • Antifungal Agents
  • Carbamates
  • Furans
  • HIV Protease Inhibitors
  • Sulfonamides
  • amprenavir
  • Erythromycin
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A
  • Ketoconazole