Late Breaker Session 6
Pharmacokinetic Interactions between Protease Inhibitors and Selected HMG-CoA Reductase Inhibitors

• LB6: Pharmacokinetic Interactions between Protease Inhibitors and Selected HMG-CoA Reductase Inhibitors (Authored by C. Fichtenbaum, J. Gerber, S. Rosenkranz, Y. Segal, T. Blaschke, J. Aberg, M. Royal, W. Burning, K. Lamb, E. Ferguson, B. Alston, F. Aweeka and the ACTG A5047 Team. Univ. of Cincinnati, OH; Univ. of Colorado Hlth. Sci. Ctr., Denver; SDAC/Harvard Sch. of Publ. Hlth., Boston, MA; Stanford Univ., Palo Alto, CA; Univ. of California, San Francisco; Washington Univ., St. Louis, MO; Frontier Science and Technology Research Fndn., Buffalo, NY; and the AACTG Operations Ctr., Rockville, MD)
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Hyperlipidemia, or elevations of cholesterol and/or triglycerides in the blood, is an adverse side effect of some antiretroviral drugs. Treatment with lipid lowering drugs, HMG-CoA reductase inhibitors ("statins"), is becoming increasingly common, despite the absence of data on drug interactions between the statins and protease inhibitors, and their possible side effects. The AIDS Clinical Trials Group (ACTG) evaluated the pharmacokinetic (PK) interactions between statins, commonly used to treat elevations of cholesterol and/or triglycerides in the blood, and the protease inhibitor combination of ritonavir (RTV) + saquinavir (SQV). (ACTG 5047.)

HIV negative adults received pravastatin 40 mg/d, simvastatin 40 mg/d or atorvastatin 40 mg/d on days 1-4 and 15-18. On days 5-18, the participants took RTV 400 mg twice a day + SQV 400 mg twice a day. Frequent blood samples on days 4 and 18 to measure the blood levels of each statin, RTV, and SQV. There were no significant adverse clinical events with simultaneous use of RTV + SQV and the statins.

Pravastatin blood levels declined about 50% in the presence of RTV + SQV. There was a significant increase in the blood levels of atorvastatin (4.5 fold) and simvastatin (31.6 fold) in the presence of RTV + SQV. The authors conclude that atorvastatin and simvastatin doses should be reduced, or these agents avoided in persons taking RTV + SQV, to avoid potential toxicity from these medications. Pravastatin dosing probably does not need adjustment in persons using RTV + SQV. (The analysis of the changes in the blood levels of RTV and SQV, with each of the statins, is still ongoing, and was not presented.)