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

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 thes e effects. Design. Open-label, randomized, balanced, single-dose, three-period crossov er study. Setting. University research center Subjects. Twelve healthy men. Intervention. Subjects received amprenavir 1200 mg, ketoconazole 400 mg, an d amprenavir 1200 mg plus ketoconazole 400 mg. Each treatment was separated by 14 days. Measurements and Main Results. Serial plasma samples for amprenavir and ket oconazole concentrations were measured by high-performance liquid chromatog raphy. Coadministration of the drugs increased amprenavir area under the cu rve extrapolated to infinity (AUC(infinity)) by 31% and reduced its maximum concentration (C-max) by 16%. Amprenavir increased the AUG, of ketoconazol e by 44% and increased the drug's half-life and C-max by 23% and 19%, respe ctively. Both agents resulted in substantial inhibition of ERMBT. Conclusion. Coadministration of ketoconazole and amprenavir results in a st atistically significant increase in AUC for both agents, but the changes ar e not likely to be clinically important.