AEGiS-13IAC: Pharmacokinetic interactions between protease inhibitors and selected HMG-CoA reductase inhibitors.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Pharmacokinetic interactions between protease inhibitors and selected HMG-CoA reductase inhibitors.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrB544)

Fichtenbaum C, Blaschke T, Rosenkranz S, Segal Y, Aberg J, Gerber J, Alston B, Lizak P, Aweeka F
C. Fichtenbaum, University of Cincinnati College of Medicine, Holmes Division, ML 0405, Eden and Bethesda Avenues, Cincinnati, OH 45267, United States, Tel.: +1 513 584 63 61, Fax: +1 513 584 60 40, E-mail: carl.fichtenbaum@uc.edu

BACKGROUND: Hyperlipidemia is an adverse effect of potent antiretroviral (protease inhibitor) therapy and treatment of lipid disorders is becoming increasingly common. In ACTG A5047, we have previously reported the effects of ritonavir (RTV) + saquinavir (SQV) on HMG-CoA reductase inhibitor (statins)levels. In this portion of ACTG A5047, we evaluated whether statins effect the levels of nelfinavir (NLF), RTV and SQV.

METHODS: HIV seronegative adults received either Pravastatin (PRA) 40 mg/d, Simvastatin 40 mg/d or Atorvastatin 40 mg/d on days 1-4 & 15-18 plus RTV 400 mg bid + SQV 400 mg bid on days 5-18; OR NLF 1250 mg bid on days 1-18 plus PRA 40 mg/d on days 15-18. Blood samples for PK analysis were obtained pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12 & 24 hours on days 4 & 18 in the RTV+SQV arms OR pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours on days 14 & 18 in the NLF group. The AUC on the 2 PK days were compared using the paired Wilcoxon signed rank test.

RESULTS: 14 subjects in each group completed both PK study days. The median estimated AUC for Nelfinavir was 24,185 and 25,590 ng /mL*hr on days 14 & 18, respectively (P = 0.54). The analyses of RTV and SQV AUCs are in progress. Adverse events typically occurred while taking protease inhibitors alone and were consistent with prior reported toxicities (e.g., GI toxicity, fatigue).

CONCLUSIONS: There was a no significant change in NLF concentrations after the addition of pravastatin. No significant unexpected adverse events occurred in subjects taking NLF+PRA or in the subjects taking RTV+SQV+other statins. Pravastatin appears to be safe for further study in persons using NLF. Results of RTV and SQV concentrations will be presented.

Keywords: AEGIS, Saquinavir, Ritonavir, Drug Interactions, Protease Inhibitors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, HIV Protease Inhibitors, Nelfinavir, Pravastatin, Anti-HIV Agents, Area Under Curve, HIV Infections, Simvastatin, Heptanoic Acids, HIV, Pyrroles, atorvastatin, Adult, pharmacokinetics
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WeOrB544