Methods: In this randomized, open-label, one-sequence crossover study, nelfinavir 1,250 mg twice a day was dosed for 17 days, followed by 14 days of nelfinavir 1,250 mg twice a day plus low doses of ritonavir of either 100 mg or 200 mg orally. Twenty-four healthy volunteers were evaluated for pharmacokinetics of nelfinavir, its metabolite M8, and ritonavir. Plasma concentrations were measured up to 12 hours after morning and evening dosing, respectively, on days 14 and 31.
Results: Ritonavir increased the area under the plasma concentration-time curve (AUC) of nelfinavir by 20 percent (p=.024) and 39 percent (p=.001) after morning and evening administration, respectively. The AUC of nelfinavir metabolite M8 was increased by 74 percent and 86 percent after morning and evening dosing (p<.001 for both).
Conclusion: During ritonavir combination therapy a clear although minor drug effect on nelfinavir pharmacokinetics was demonstrated but no dose effect was shown. [M. Kurowski et al.; Clin Pharmacol Ther, 2002 Aug;72:123-32.]