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Keywords:

  • hard gelatin capsule;
  • pharmacokinetics;
  • ritonavir;
  • saquinavir;
  • soft gelatin capsule

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 × 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 µg/mL/h was reported for the HGC formulation compared with 11.655 µg/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.