Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin.
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Hulskotte EG, Feng HP, Xuan F, Gupta S, van Zutven MG, O'Mara E, Wagner JA, Butterton JR
Pharmacokinetic evaluation of the interaction between hepatitis C virus protease inhibitor boceprevir and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pravastatin.
Antimicrob Agents Chemother. 2013 Jun;57(6):2582-8. doi: 10.1128/AAC.02347-12. Epub 2013 Mar 25.
- PubMed ID
- 23529734 [ View in PubMed]
- Abstract
Boceprevir is a potent orally administered inhibitor of hepatitis C virus and a strong, reversible inhibitor of CYP3A4, the primary metabolic pathway for many 3-hydroxy-3-methylglutaryl coenzyme A (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 with 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 area under the concentration-time curve from time zero to infinity after single dosing (AUC(inf)) increasing 2.3-fold (90% confidence interval [CI], 1.85, 2.90) and maximum observed concentration in plasma (Cmax) 2.7-fold (90% CI, 1.81, 3.90). Pravastatin exposure was slightly increased in the presence of boceprevir, with pravastatin AUC(inf) increasing 1.63-fold (90% CI, 1.03, 2.58) and C(max) 1.49-fold (90% CI, 1.03, 2.14). Boceprevir exposure was generally unchanged when the drug was 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.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Boceprevir Cytochrome P450 3A4 Protein Humans UnknownSubstrateInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareAtorvastatinRoxithromycin The metabolism of Atorvastatin can be decreased when combined with Roxithromycin. AtorvastatinDirithromycin The metabolism of Atorvastatin can be decreased when combined with Dirithromycin. AtorvastatinCandicidin The metabolism of Atorvastatin can be decreased when combined with Candicidin. AtorvastatinEverolimus The metabolism of Atorvastatin can be decreased when combined with Everolimus. AtorvastatinEpothilone D The metabolism of Atorvastatin can be decreased when combined with Epothilone D.