Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin.

摘要: ABSTRACT Boceprevir is a potent orally administered inhibitor of hepatitis C virus and strong, reversible CYP3A4, the primary metabolic pathway for many 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Thus, aim present study was to investigate drug-drug interactions between atorvastatin or pravastatin boceprevir. We conducted single-center, open-label, fixed-sequence, one-way-crossover with 20 healthy adult volunteers. Subjects received single-dose (40 mg) on day 1, followed by boceprevir (800 mg three times daily) 7 10 days. Repeat single doses were in presence steady-state Atorvastatin exposure increased boceprevir, area under concentration-time curve from time zero infinity after dosing (AUC inf ) increasing 2.3-fold (90% confidence interval [CI], 1.85, 2.90) maximum observed concentration plasma ( max 2.7-fold CI, 1.81, 3.90). Pravastatin slightly AUC 1.63-fold 1.03, 2.58) 1.49-fold 2.14). generally unchanged when drug coadministered pravastatin. All adverse events mild consistent known safety profile The 130% increase supports use lowest possible effective dose without exceeding daily 40 mg. 60% coadministration initiation treatment at recommended close clinical monitoring.