Setrobuvir

RNA-directed RNA polymerase inhibitor treatment of hepatitis C virus infection

L. Kapelusznik, E. L. Heil, Zelalem Temesgen, R. Talwani

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Setrobuvir is a non-nucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 RNA-directed RNA polymerase (NS5B) that allosterically binds the Palm I site of the enzyme. The usual dose is 200 mg twice daily after an initial loading dose of 800 mg. Its elimination half-life ranges from 22 to 31 hours, with biliary excretion being the major route of elimination. In vitro studies demonstrated that setrobuvir retains activity against multiple common mutations of other drug classes, and conversely, drugs from several other classes are effective against setrobuvir-resistant viruses. Setrobuvir produces a rapid decline in the HCV viral load, but if given as monotherapy, HCV often rapidly selects for resistance. In combination with pegylated interferon (peg-IFN) and ribavirin, setrobuvir increases the proportion of HCV undetectable treatment-naive and -experienced patients at week 12 compared to those treated with peg-IFN, ribavirin and placebo. Subjects with the favorable IL28B CC allele who receive peg-IFN and ribavirin have a slower but comparable response compared to those who receive setrobuvir, but the addition of this drug substantially increases the response of patients with the CT/TT allele. Rash is the only notable effect compared to placebo, and setrobuvir appears to have minimal impact on hematological parameters, as it did not exacerbate anemia or leukopenia in the clinical trials performed to date.

Original languageEnglish (US)
Pages (from-to)725-733
Number of pages9
JournalDrugs of the Future
Volume37
Issue number10
DOIs
StatePublished - 2012

Fingerprint

RNA Replicase
Virus Diseases
Hepacivirus
Ribavirin
Interferons
Therapeutics
Alleles
Placebos
Pharmaceutical Preparations
Leukopenia
setrobuvir
Exanthema
Viral Load
Half-Life
Anemia
Genotype
Clinical Trials
Viruses
Mutation
Enzymes

Keywords

  • ANA-598
  • RG-7790
  • RNA-directed RNA polymerase inhibitor
  • Setrobuvir
  • Treament of hepatitis

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Setrobuvir : RNA-directed RNA polymerase inhibitor treatment of hepatitis C virus infection. / Kapelusznik, L.; Heil, E. L.; Temesgen, Zelalem; Talwani, R.

In: Drugs of the Future, Vol. 37, No. 10, 2012, p. 725-733.

Research output: Contribution to journalArticle

Kapelusznik, L. ; Heil, E. L. ; Temesgen, Zelalem ; Talwani, R. / Setrobuvir : RNA-directed RNA polymerase inhibitor treatment of hepatitis C virus infection. In: Drugs of the Future. 2012 ; Vol. 37, No. 10. pp. 725-733.
@article{80d659db39794d0eb16189453c60f44b,
title = "Setrobuvir: RNA-directed RNA polymerase inhibitor treatment of hepatitis C virus infection",
abstract = "Setrobuvir is a non-nucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 RNA-directed RNA polymerase (NS5B) that allosterically binds the Palm I site of the enzyme. The usual dose is 200 mg twice daily after an initial loading dose of 800 mg. Its elimination half-life ranges from 22 to 31 hours, with biliary excretion being the major route of elimination. In vitro studies demonstrated that setrobuvir retains activity against multiple common mutations of other drug classes, and conversely, drugs from several other classes are effective against setrobuvir-resistant viruses. Setrobuvir produces a rapid decline in the HCV viral load, but if given as monotherapy, HCV often rapidly selects for resistance. In combination with pegylated interferon (peg-IFN) and ribavirin, setrobuvir increases the proportion of HCV undetectable treatment-naive and -experienced patients at week 12 compared to those treated with peg-IFN, ribavirin and placebo. Subjects with the favorable IL28B CC allele who receive peg-IFN and ribavirin have a slower but comparable response compared to those who receive setrobuvir, but the addition of this drug substantially increases the response of patients with the CT/TT allele. Rash is the only notable effect compared to placebo, and setrobuvir appears to have minimal impact on hematological parameters, as it did not exacerbate anemia or leukopenia in the clinical trials performed to date.",
keywords = "ANA-598, RG-7790, RNA-directed RNA polymerase inhibitor, Setrobuvir, Treament of hepatitis",
author = "L. Kapelusznik and Heil, {E. L.} and Zelalem Temesgen and R. Talwani",
year = "2012",
doi = "10.1358/dof.2012.037.010.1840394",
language = "English (US)",
volume = "37",
pages = "725--733",
journal = "Drugs of the Future",
issn = "0377-8282",
publisher = "Prous Science",
number = "10",

}

TY - JOUR

T1 - Setrobuvir

T2 - RNA-directed RNA polymerase inhibitor treatment of hepatitis C virus infection

AU - Kapelusznik, L.

AU - Heil, E. L.

AU - Temesgen, Zelalem

AU - Talwani, R.

PY - 2012

Y1 - 2012

N2 - Setrobuvir is a non-nucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 RNA-directed RNA polymerase (NS5B) that allosterically binds the Palm I site of the enzyme. The usual dose is 200 mg twice daily after an initial loading dose of 800 mg. Its elimination half-life ranges from 22 to 31 hours, with biliary excretion being the major route of elimination. In vitro studies demonstrated that setrobuvir retains activity against multiple common mutations of other drug classes, and conversely, drugs from several other classes are effective against setrobuvir-resistant viruses. Setrobuvir produces a rapid decline in the HCV viral load, but if given as monotherapy, HCV often rapidly selects for resistance. In combination with pegylated interferon (peg-IFN) and ribavirin, setrobuvir increases the proportion of HCV undetectable treatment-naive and -experienced patients at week 12 compared to those treated with peg-IFN, ribavirin and placebo. Subjects with the favorable IL28B CC allele who receive peg-IFN and ribavirin have a slower but comparable response compared to those who receive setrobuvir, but the addition of this drug substantially increases the response of patients with the CT/TT allele. Rash is the only notable effect compared to placebo, and setrobuvir appears to have minimal impact on hematological parameters, as it did not exacerbate anemia or leukopenia in the clinical trials performed to date.

AB - Setrobuvir is a non-nucleoside inhibitor of the hepatitis C virus (HCV) genotype 1 RNA-directed RNA polymerase (NS5B) that allosterically binds the Palm I site of the enzyme. The usual dose is 200 mg twice daily after an initial loading dose of 800 mg. Its elimination half-life ranges from 22 to 31 hours, with biliary excretion being the major route of elimination. In vitro studies demonstrated that setrobuvir retains activity against multiple common mutations of other drug classes, and conversely, drugs from several other classes are effective against setrobuvir-resistant viruses. Setrobuvir produces a rapid decline in the HCV viral load, but if given as monotherapy, HCV often rapidly selects for resistance. In combination with pegylated interferon (peg-IFN) and ribavirin, setrobuvir increases the proportion of HCV undetectable treatment-naive and -experienced patients at week 12 compared to those treated with peg-IFN, ribavirin and placebo. Subjects with the favorable IL28B CC allele who receive peg-IFN and ribavirin have a slower but comparable response compared to those who receive setrobuvir, but the addition of this drug substantially increases the response of patients with the CT/TT allele. Rash is the only notable effect compared to placebo, and setrobuvir appears to have minimal impact on hematological parameters, as it did not exacerbate anemia or leukopenia in the clinical trials performed to date.

KW - ANA-598

KW - RG-7790

KW - RNA-directed RNA polymerase inhibitor

KW - Setrobuvir

KW - Treament of hepatitis

UR - http://www.scopus.com/inward/record.url?scp=84952978638&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84952978638&partnerID=8YFLogxK

U2 - 10.1358/dof.2012.037.010.1840394

DO - 10.1358/dof.2012.037.010.1840394

M3 - Article

VL - 37

SP - 725

EP - 733

JO - Drugs of the Future

JF - Drugs of the Future

SN - 0377-8282

IS - 10

ER -