The summaries are free for public
use. The Chronic Liver Disease
Foundation will continue to add and
archive summaries of articles deemed
relevant to CLDF by the Board of
Trustees and its Advisors.
Abstract Details
Pharmacokinetic Evaluation of the Interaction Between the HCV Protease Inhibitor Boceprevir and the HMG-CoA Reductase Inhibitors Atorvastatin and Pravastatin
Hulskotte E, Feng HP, Xuan F, Gupta S, van Zutven M, O'Mara E, Wagner J, Butterton J. Antimicrob Agents Chemother. 2013 Mar 25. [Epub ahead of print]
Source
Merck Sharp & Dohme Corp, Molenstraat 110, 5342 CC Oss, The Netherlands.
Abstract
Boceprevir is a potent orally administered inhibitor of the hepatitis C virus and a strong, reversible inhibitor of CYP3A4, the primary metabolic pathway for many HMG-CoA reductase inhibitors. Thus, the aim of the present study was to investigate drug-drug interactions between atorvastatin or pravastatin, and boceprevir. We conducted a single-center, open-label, fixed-sequence, one-way crossover study in 20 healthy adult volunteers. Subjects received single-dose atorvastatin (40 mg) or pravastatin (40 mg) on day 1 followed by boceprevir (800 mg three times daily) for 7 to 10 days. Repeat single doses of atorvastatin or pravastatin were administered in the presence of steady-state boceprevir. Atorvastatin exposure increased in the presence of boceprevir, with atorvastatin AUCinf increasing 2.3-fold (90% confidence interval [CI] 1.85, 2.90) and Cmax 2.7-fold (90% CI 1.81, 3.90). Pravastatin exposure was slightly increased in the presence of boceprevir, with pravastatin AUCinf increasing 1.63-fold (90% CI 1.03, 2.58) and Cmax 1.49-fold (90% CI 1.03, 2.14). Boceprevir exposure was generally unchanged when coadministered with atorvastatin or pravastatin. All adverse events were mild and consistent with the known safety profile of boceprevir. The observed 130% increase in AUC of atorvastatin supports the use of the lowest possible effective dose of atorvastatin when coadministered with boceprevir, without exceeding a maximum daily dose of 40 mg. The observed 60% increase in pravastatin AUC with boceprevir coadministration supports the initiation of pravastatin treatment at the recommended dose when coadministered with boceprevir, with close clinical monitoring.