Clinical pharmacology profile of boceprevir, a hepatitis C virus NS3 protease inhibitor: focus on drug-drug interactions.

Abstract

Boceprevir is a potent, orally administered ketoamide inhibitor that targets the active site of the hepatitis C virus (HCV) non-structural (NS) 3 protease. The addition of boceprevir to peginterferon plus ribavirin resulted in higher rates of sustained virologic response (SVR) than for peginterferon plus ribavirin alone in phase III studies in both previously treated and untreated patients with HCV infection. Because boceprevir is metabolized by metabolic routes common to many other drugs, and is an inhibitor of cytochrome P450 (CYP) 3A4/5, there is a high potential for drug-drug interactions when boceprevir is administered with other therapies, particularly when treating patients with chronic HCV infection who are often receiving other medications concomitantly. Boceprevir is no longer widely used in the US or EU due to the introduction of second-generation treatments for HCV infection. However, in many other geographic regions, first-generation protease inhibitors such as boceprevir continue to form an important treatment option for patients with HCV infection. This review summarizes the interactions between boceprevir and other therapeutic agents commonly used in this patient population, indicating dose adjustment requirements where needed. Most drug interactions do not affect boceprevir plasma concentrations to a clinically meaningful extent, and thus efficacy is likely to be maintained when boceprevir is coadministered with the majority of other therapeutics. Overall, the drug-drug interaction profile of boceprevir suggests that this agent is suitable for use in a wide range of HCV-infected patients receiving concomitant therapies.

• Authors: Sauzanne Khalilieh, Hwa-Ping Feng, Ellen G J Hulskotte, Larissa A Wenning, Joan R Butterton
• Journal: Clinical pharmacokinetics (Clin Pharmacokinet) Vol. 54 Issue 6 Pg. 599-614 (Jun 2015) ISSN: 1179-1926 [Electronic] Switzerland
• PMID: 25787025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antiviral Agents
• NS3 protein, hepatitis C virus
• Protease Inhibitors
• Viral Nonstructural Proteins
• Ribavirin
• N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide
• Proline

Topics

• Animals
• Antiviral Agents (pharmacology)
• Drug Interactions
• Drug Therapy, Combination
• Hepatitis C, Chronic (drug therapy)
• Humans
• Proline (analogs & derivatives, pharmacokinetics, pharmacology)
• Protease Inhibitors (pharmacokinetics, pharmacology)
• Randomized Controlled Trials as Topic
• Ribavirin (pharmacology)
• Treatment Outcome
• Viral Load (drug effects)
• Viral Nonstructural Proteins (antagonists & inhibitors)