title: Emerging therapeutic options for the management of hepatitis C infection.
abstract: Until recently the traditional treatment for hepatitis C infection included pegylated interferon and ribavirin combination therapy. The sustained virological response (SVR) seen with this combination is poor and requires lengthy treatment to achieve. Additionally, significant side effects and numerous contraindications prevented many patients from being successfully treated with this therapy. In 2011, two new protease inhibitors, telaprevir and boceprevir, were approved for use with pegylated interferon and ribavirin in the United States by the United States Food and Drug Administration. These agents have significantly improved SVR rates; however significant problems with toxicity remain including severe skin rash and neutropenia. There are a wide range of compounds in late stage development for the future treatment of hepatitis C that exploit many different mechanisms of viral inhibition. Some of these compounds include additional protease inhibitors, like telaprevir and boceprevir, as well as inhibitors of other nonstructural proteins in the viral genome such as NS5A and NS5B, and compounds that target host proteins within the virus. Some of these agents are being developed for oral administration once daily and various combinations are being assessed for use without the need for pegylated interferon and ribavirin. This paper reviews agents in late phase development that may be commercially available within 1-2 years.
authors: J Richard Thompson, Department of Pharmacy Practice, One University Park Drive, Lipscomb University College of Pharmacy, Nashville, TN 37204, United States.
authors: J Richard
authors: JR
authors: Thompson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development; D006526:Hepatitis C / Q000175:diagnosis / Q000188:drug therapy*; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D058990:Molecular Targeted Therapy; D009842:Oligopeptides / Q000009:adverse effects / Q000627:therapeutic use*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016896:Treatment Outcome; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D011480:Protease Inhibitors; D017361:Viral Nonstructural Proteins; C486464:telaprevir; 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; D011392:Proline; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
keywords: Cyclophilin inhibitors; Hepatitis C; Interferon; Pharmacotherapy; Polymerase inhibitors; Protease inhibitors; Ribavirin