Low-dose ritonavir moderately enhances nelfinavir exposure

The protease inhibitor ritonavir is increasingly administered at subtherapeutic doses in highly active antiretroviral treatment, to utilize its potential for drug interactions and to enhance the plasma concentrations of other concomitantly prescribed protease inhibitors. The addition of low doses of ritonavir to nelfinavir was investigated to describe the extent of pharmacokinetic interaction.

In this randomized, open-label, one-sequence crossover study, nelfinavir 1250 mg twice a day was dosed for 17 days, followed by 14 days of nelfinavir 1250 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.

Ritonavir increased the area under the plasma concentration-time curve (AUC) of nelfinavir by 20% (P =.024) and 39% (P =.001) after morning and evening administration, respectively. The AUC of nelfinavir metabolite M8 was increased by 74% and 86% after morning and evening dosing (P <.001 for both).

During ritonavir combination therapy a clear although minor drug effect on nelfinavir pharmacokinetics was demonstrated but no dose effect was shown.