A Pharmacokinetic–Viral Kinetic Model Describes the Effect of Alisporivir as Monotherapy or in Combination With Peg‐IFN on Hepatitis C Virologic Response. Issue 5 (28th August 2014)

• Record Type: Journal Article
• Authors: Nguyen, T H T; Mentré, F; Levi, M; Yu, J; Guedj, J
• Is Part Of: Clinical pharmacology & therapeutics. Volume 96:Issue 5(2014)
• Page Start: 599
• Page End: 608
• Publication Date: 2014-08-28
• Subjects: Pharmacology -- Periodicals; Therapeutics -- Periodicals; 615.5
• DOI: 10.1038/clpt.2014.173
• Languages: English
• ISSNs: 0009-9236

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Alisporivir is a cyclophilin inhibitor with demonstrated <italic>in vitro</italic> and <italic>in vivo</italic> activity against hepatitis C virus (HCV). We estimated the antiviral effectiveness of alisporivir alone or in combination with pegylated interferon (peg‐IFN) in 88 patients infected with different HCV genotypes treated for 4 weeks. The pharmacokinetics of the two drugs were modeled and used as driving functions for the viral kinetic model. Genotype was found to significantly affect peg‐IFN effectiveness (ɛ = 86.3 and 99.1% for genotypes 1/4 and genotypes 2/3, respectively, <italic>P</italic> < 10<sup>−7</sup>) and the loss rate of infected cells (δ = 0.22 vs. 0.39 per day in genotype 1/4 and genotype 2/3 patients, respectively, <italic>P</italic> < 10<sup>−6</sup>). Alisporivir effectiveness was not significantly different across genotypes and was high for doses ≥600 mg q.d. We simulated virologic responses with other alisporivir dosing regimens in HCV genotype 2/3 patients using the model. Our predictions consistently matched the observed responses, demonstrating that this model could be a useful tool for anticipating virologic response and optimizing alisporivir‐based therapies.</p> <p> <italic>Clinical Pharmacology & Therapeutics</italic> (2014); <bold>96</bold> 5, 599–608. doi:<ext-link ext-link-type="doi" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">10.1038/clpt.2014.173</ext-link></p> </abstract>