To evaluate the pharmacokinetic compatibility of a ritonavir-boosted indinavir-fosamprenavir combination among patients with human immunodeficiency virus (HIV).
Single-center, nonrandomized, prospective, multiple-dose, two-phase pharmacokinetic study.
University research center.
Eight adult patients with HIV infection who had been receiving and tolerating indinavir 800 mg–ritonavir 100 mg twice/day for at least 2 weeks.
After 12-hour pharmacokinetic sampling was performed on all patients (period A), fosamprenavir (a prodrug of amprenavir) 700 mg twice/day was coadministered for 5 days, with a repeat 12-hour pharmacokinetic sampling performed on the fifth day (period B).
Measurements and Main Results
Pharmacokinetic parameters were determined for indinavir, ritonavir, and amprenavir: area under the concentration-time curve from time 0 to 12 hours after dosing (AUC0–12), maximum plasma concentration (Cmax), and 12-hour plasma concentration (C12). For each parameter, the geometric mean, as well as the geometric mean ratio (GMR) comparing period B with period A, were calculated. Indinavir Cmax was lowered by 20% (GMR 0.80, 95% confidence interval [CI] 0.67–0.96), AUC0–12 was lowered by 6% (GMR 0.94, 95% CI 0.74–1.21), and C12 was increased by 28% (GMR 1.28, 95% CI 0.78–2.10). Ritonavir AUC0–12 was 20% lower (GMR 0.80, 95% CI 0.54–1.19), Cmax was 15% lower (GMR 0.85, 95% CI 0.55–1.32), and C12 was 7% lower (GMR 0.93, 95% CI 0.49–1.76). With the exception of indinavir Cmax, the changes in indinavir and ritonavir pharmacokinetic parameters observed after fosamprenavir coadministration were not statistically significant. The geometric means of amprenavir AUC0–12, Cmax, and C12 were 41,517 ng•hour/ml (95% CI 30,317–56,854 ng•hr/ml), 5572 ng/ml (95% CI 4330–7170 ng/ml), and 2421 ng/ml (95% CI 1578–3712 ng/ml), respectively.
The combination of indinavir 800 mg–ritonavir 100 mg–fosamprenavir 700 mg twice/day appears to be devoid of a clinically significant drug-drug interaction and should be evaluated as an alternative regimen in salvage HIV treatment. This combination may be suitable as part of a background regimen to optimize the therapeutic benefit of newer classes of antiretroviral agents such as the integrase and coreceptor inhibitors in the treatment of multidrug-resistant viruses.