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Pharmacokinetics of Saquinavir With Atazanavir or Low-Dose Ritonavir Administered Once Daily (ASPIRE I) or Twice Daily (ASPIRE II) in Seronegative Volunteers

From the University of Alabama at Birmingham, School of Medicine, Division of Clinical Pharmacology (Dr King, Dr Acosta); Tibotec, Inc, Yardley, Pennsylvania (Dr Kakuda); PPD, Inc, Menlo Park, California (Ms Paul); CPMC Research Institute, San Francisco, California (Mr Tse); and AnorMED, Inc, Langley, British Columbia (Dr Becker).

ASPIRE I and II were prospective, 3-way sequential crossover studies in healthy volunteers to compare the safety and pharmacokinetics of saquinavir/ritonavir (SQV/RTV) with saquinavir/atazanavir (SQV/ATV) administered either once daily (QD, ASPIRE I) or twice daily (BID, ASPIRE II). Treatments were separated by 10 days, and pharmacokinetic analyses were performed on days 11, 32, and 53. SQV pharmacokinetics were significantly higher when dosed with RTV compared to ATV (P < .05 for all comparisons). ATV pharmacokinetics were similar within treatment arms. ATV C_min increased approximately 60%, and C_max decreased approximately 35% with BID dosing compared with QD dosing. Women had higher exposure for all 3 protease inhibitors (PIs) compared with men after adjusting for weight. Adverse effects were primarily gastrointestinalrelated with SQV/RTV and hyperbilirubinemia with SQV/ATV. Although SQV plasma concentrations were higher when coadministered with RTV, a combination of SQV/ATV administered BID may be a viable alternative in HIV-infected, PI-naive subjects intolerant to RTV.

Key Words: HIV protease inhibitors • saquinavir • ritonavir • atazanavir • pharmacokinetics

Address for reprints: Address for correspondence: Jennifer R. King, PharmD, University of Alabama at Birmingham, Division of Clinical Pharmacology, 1530 3rd Avenue South, VH 116, Birmingham, AL 35294-0019.

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