title: Boceprevir: a protease inhibitor for the treatment of chronic hepatitis C.
abstract: OBJECTIVE
  To review the pharmacology, pharmacokinetics, safety, and efficacy of boceprevir, a novel oral hepatitis C virus (HCV) nonstructural 3 (NS3) protease inhibitor for the treatment of chronic HCV infection, specifically, genotype 1.
  
  
  METHODS
  A literature search was conducted through MEDLINE and EMBASE (1966-May 2011) using the terms boceprevir and SCH 503034. Data from the package insert, abstracts obtained from conferences, and unpublished Phase 2-3 clinical trials, obtained through clinicaltrials.gov, were also reviewed.
  
  
  METHODS
  All English-language articles identified from the data sources were evaluated. References from selected articles were used to identify other pertinent citations. Article selection focused on pharmacology, clinical trials, safety analyses, and resistance. Preference was given to human data.
  
  
  RESULTS
  Boceprevir is an oral protease inhibitor that binds to the NS3 protein of HCV, ultimately inhibiting viral intracellular replication. Boceprevir displays linear pharmacokinetics and is rapidly absorbed upon oral administration. In clinical studies of treatment-naïve and treatment-experienced patients, boceprevir, in combination with standard of care (pegylated interferon [Peg-IFN]-α-2b with or without ribavirin) achieved greater sustained viral response (SVR) rates compared to standard of care. Safety analyses showed an increased incidence of adverse effects when boceprevir was used with Peg-IFN-α-2b and ribavirin. The most common adverse events reported include fatigue, headache, nausea, dysguesia, and anemia; the incidence of the latter 2 adverse effects may be increased if boceprevir is added to standard therapy. Additional Phase 2 and 3 studies are currently enrolling participants.
  
  
  CONCLUSIONS
  Boceprevir should be used in combination with Peg-IFN-α-2b and ribavirin in the treatment of chronic HCV genotype 1 infection. The improved response rates achieved with that combination will make boceprevir a viable option compared with other developing and approved NS3 protease inhibitors for treatment-naïve and treatment-experienced nonresponders/relapsers. Additional data are needed to clarify the potential for resistance and drug interactions.
authors.affiliation: Department of Pharmacy Practice, School of Pharmacy Worcester/Manchester, Massachusetts College of Pharmacy and Health Sciences, Worcester, MA, USA. Bryce.Foote@mcphs.edu
authors.forename: Bryce S
authors.initials: BS
authors.lastname: Foote
authors.forename: Linda M
authors.initials: LM
authors.lastname: Spooner
authors.forename: Paul P
authors.initials: PP
authors.lastname: Belliveau
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011392:Proline; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C512204: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; C417083:peginterferon alfa-2b