Pharmacokinetic and tolerability profile of twice-daily saquinavir hard gelatin capsules and saquinavir soft gelatin capsules boosted with ritonavir in healthy volunteers

Abstract

Objective: To evaluate the pharmacokinetics and safety of a boosted saquinavir (SQV)/ritonavir (RTV) combination, administered as either the hard gelatin capsule (HGC) or soft gelatin capsule (SGC) formulation of SQV, in 24 healthy volunteers.

Methods: This was a single-centre, open-label, randomized, 2 x 2 crossover study. Twelve subjects were randomized to receive SQV/RTV 1000 mg/100 mg twice daily (BID) orally for 10 days, as either the HGC or SGC formulation. The pharmacokinetic profile of SQV was determined on day 10. Subjects then crossed over to the opposite SQV formulation, and the pharmacokinetic profile was determined again on day 20. The primary analysis was the assessment of bioequivalence based on logarithmically transformed values for AUC(0-24 h) and Cmax for the two formulations.

Results: There was a statistically significant increase in the geometric means of all the pharmacokinetic variables evaluated for SQV-HGC/RTV compared with SQV-SGC/RTV. A mean AUC0-24 h-value of 15.798 micro g/mL/h was reported for the HGC formulation compared with 11.655 micro g/mL/h for the SGC formulation (P = 0.0043). The SQV-HGC/RTV combination was better tolerated in terms of gastrointestinal system disorders. Furthermore, no elevations in triglycerides or total cholesterol were reported with SQV/RTV during the entire study period.

Conclusion: In healthy volunteers, RTV boosting of SQV-HGC produces plasma exposures at least comparable to SQV-SGC, which is accompanied by an improvement in gastrointestinal system disorders.