Literature DB >> 29228392

Hepatic Pharmacokinetics and Pharmacodynamics With Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir Treatment and Variable Ribavirin Dosage.

Andrew H Talal1, Emily O Dumas2, Barbara Bauer1, Richard M Rejman1, Andrew Ocque1, Gene D Morse1, Danijela Lucic3, Gavin A Cloherty3, Jennifer King4, Jiuhong Zha2, Hongtao Zhang2, Daniel E Cohen2, Nancy Shulman2, Jean-Michel Pawlotsky5,6, Christophe Hézode6,7.   

Abstract

Background: It is unknown whether ribavirin (RBV) coadministration modifies the early rate of decline of hepatitis C virus (HCV) RNA in the liver versus plasma compartments, specifically.
Methods: This partially randomized, open-label, phase 2 study enrolled treatment-naive, noncirrhotic patients with HCV genotype 1a. Patients were randomized 1:1 into Arms A and B, and then enrolled in Arm C. Patients received ombitasvir/paritaprevir/ritonavir plus dasabuvir for 12 weeks with either: no RBV for the first 2 weeks followed by weight-based dosing thereafter (Arm A), weight-based RBV for all 12 weeks (Arm B), or low-dose RBV (600 mg) once daily for all 12 weeks. Fine needle aspiration (FNA) was used to determine HCV RNA decline within liver.
Results: Baseline HCV RNA was higher and declined more rapidly in plasma than liver; however, RBV dosing did not impact either median plasma or liver HCV RNA decline during the first 2 weeks of treatment. Liver-to-plasma drug concentrations were variable over time. The most common adverse event was pain associated with FNA. Conclusions: Coadministration of RBV had minimal visible impact on the plasma or liver kinetics of HCV RNA decline during the first 2 weeks of treatment, regardless of RBV dosing.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Entities:  

Keywords:  fine needle aspiration; hepatitis C virus; pharmacodynamics; ribavirin; viral kinetics

Mesh:

Substances:

Year:  2018        PMID: 29228392      PMCID: PMC5853515          DOI: 10.1093/infdis/jix495

Source DB:  PubMed          Journal:  J Infect Dis        ISSN: 0022-1899            Impact factor:   5.226


  34 in total

1.  Sustained virologic response of 100% in HCV genotype 1b patients with cirrhosis receiving ombitasvir/paritaprevir/r and dasabuvir for 12weeks.

Authors:  Jordan J Feld; Christophe Moreno; Roger Trinh; Edward Tam; Stefan Bourgeois; Yves Horsmans; Magdy Elkhashab; David E Bernstein; Ziad Younes; Robert W Reindollar; Lois Larsen; Bo Fu; Kevin Howieson; Akshanth R Polepally; Andreas Pangerl; Nancy S Shulman; Fred Poordad
Journal:  J Hepatol       Date:  2015-10-22       Impact factor: 25.083

2.  Ultra-performance liquid chromatography tandem mass spectrometry for determination of Direct Acting Antiviral drugs in human liver fine needle aspirates.

Authors:  Andrew J Ocque; Colleen E Hagler; Robin DiFrancesco; Gene D Morse; Andrew H Talal
Journal:  J Chromatogr B Analyt Technol Biomed Life Sci       Date:  2017-03-24       Impact factor: 3.205

3.  ABT-450/r-ombitasvir and dasabuvir with or without ribavirin for HCV.

Authors:  Peter Ferenci; David Bernstein; Jacob Lalezari; Daniel Cohen; Yan Luo; Curtis Cooper; Edward Tam; Rui T Marinho; Naoky Tsai; Anders Nyberg; Terry D Box; Ziad Younes; Pedram Enayati; Sinikka Green; Yaacov Baruch; Bal Raj Bhandari; Florin Alexandru Caruntu; Thomas Sepe; Vladimir Chulanov; Ewa Janczewska; Giuliano Rizzardini; Judit Gervain; Ramon Planas; Christophe Moreno; Tarek Hassanein; Wangang Xie; Martin King; Thomas Podsadecki; K Rajender Reddy
Journal:  N Engl J Med       Date:  2014-05-04       Impact factor: 91.245

4.  Modelling how ribavirin improves interferon response rates in hepatitis C virus infection.

Authors:  Narendra M Dixit; Jennifer E Layden-Almer; Thomas J Layden; Alan S Perelson
Journal:  Nature       Date:  2004-12-16       Impact factor: 49.962

Review 5.  Clinical Pharmacokinetics of Dasabuvir.

Authors:  Jennifer R King; Jiuhong Zha; Amit Khatri; Sandeep Dutta; Rajeev M Menon
Journal:  Clin Pharmacokinet       Date:  2017-10       Impact factor: 6.447

6.  Impact of all oral anti-hepatitis C virus therapy: A meta-analysis.

Authors:  Siddharth Bansal; Ashwani K Singal; Brendan M McGuire; Bhupinder S Anand
Journal:  World J Hepatol       Date:  2015-04-18

7.  Interferon regulatory factor-3 activation, hepatic interferon-stimulated gene expression, and immune cell infiltration in hepatitis C virus patients.

Authors:  Daryl T-Y Lau; Penny Mar Fish; Mala Sinha; David M Owen; Stanley M Lemon; Michael Gale
Journal:  Hepatology       Date:  2008-03       Impact factor: 17.425

8.  Retreatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.

Authors:  Stefan Zeuzem; Ira M Jacobson; Tolga Baykal; Rui T Marinho; Fred Poordad; Marc Bourlière; Mark S Sulkowski; Heiner Wedemeyer; Edward Tam; Paul Desmond; Donald M Jensen; Adrian M Di Bisceglie; Peter Varunok; Tarek Hassanein; Junyuan Xiong; Tami Pilot-Matias; Barbara DaSilva-Tillmann; Lois Larsen; Thomas Podsadecki; Barry Bernstein
Journal:  N Engl J Med       Date:  2014-04-10       Impact factor: 91.245

9.  Antiviral action of ribavirin in chronic hepatitis C.

Authors:  Jean-Michel Pawlotsky; Harel Dahari; Avidan U Neumann; Christophe Hezode; Georgios Germanidis; Isabelle Lonjon; Laurent Castera; Daniel Dhumeaux
Journal:  Gastroenterology       Date:  2004-03       Impact factor: 22.682

10.  Hepatitis C virus RNA-dependent RNA polymerase (NS5B) as a mediator of the antiviral activity of ribavirin.

Authors:  D Maag; C Castro; Z Hong; C E Cameron
Journal:  J Biol Chem       Date:  2001-10-15       Impact factor: 5.157

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  1 in total

1.  Intrahepatic Viral Kinetics During Direct-Acting Antivirals for Hepatitis C in Human Immunodeficiency Virus Coinfection: The AIDS Clinical Trials Group A5335S Substudy.

Authors:  Ashwin Balagopal; Laura M Smeaton; Jeffrey Quinn; Charles S Venuto; Gene D Morse; Vincent Vu; Beverly Alston-Smith; Daniel E Cohen; Jorge L Santana-Bagur; Donald D Anthony; Mark S Sulkowski; David L Wyles; Andrew H Talal
Journal:  J Infect Dis       Date:  2020-07-23       Impact factor: 7.759

  1 in total

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