This a Phase I, multiple-dose, four arm, drug interaction pharmacokinetic study. The sample size is a follow: Arm A1: 14 evaluable HIV-seronegative, healthy subject, Arm A2: 14 evaluable HIV-seronegative, healthy subjects Arm A3: 14. evaluable HIV-seronegative, healthy subjects, Arm B: 14 evaluable HIV-seronegative, healthy subjects. The subjects will be randomly assigned to one of the following arms: Arm A: Arm A1: Days 1-4: Give pravastatin (40 mg po q am) only, Days 5-7: Discontinue pravastatin, start ritonavir (300 mg po bid) + saquinavir (400 mg po bid), Days 8-14: Increase ritonavir (400 mg po bid ) + continue saquinavir (400 mg po bid), Days 15-18: Continue ritonavir (400 mg po bid) + saquinavir (400 mg po bid); add pravastatin (40 mg po q am). Arm A2: Days 1-4: Give simvastatin (40 mg po q am) only Day 5-7: Discontinue simvastatin, start ritonavir (300 mg po bid)+ saquinavir (400 mg po bid), Days 8-14: Increase ritonavir (400 mg po bid)+ continue saquinavir (400 mg po bid), Days 15-18: Continue ritonavir (400 mg po bid); add simvastatin (40 mg po q am). Arm A3: Days 1-4: Give atorvastatin (40 mg po q am) only, Days 5-7: Discontinue atorvastatin, start ritonavir (300mg po bid)+ saquinavir (400 mg po bid), Days 8-14: Increase ritonavir (400 mg po bid)+continue saquinavir (400 mg po bid), Days 15-18: Continue ritonavir (400 mg po bid)+saquinavir (400 mg po bid); add atrovastatin (40 mg po q am). Arm B: Days 1-14: Give Nelfinavir (1250 mg po q 12h)only, Days 15-18: Continue nelfinavir (1250 mg po q 12h), add pravastatin (40mg po q am). The study is expected to last 25 days. The objectives are 1) Investigate the effect of ritonavir (RTV) and saquinavir (SQV) on the Pharmacokinetics of pravastatin, simvastatin, and atorvastatin; 2) Evaluate the effect of pravastatin on the disposition of nelfinavir and its M8 metabolite.
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