A pharmacokinetic-viral kinetic model describes the effect of alisporivir as monotherapy or in combination with peg-IFN on hepatitis C virologic response.

Abstract

Alisporivir is a cyclophilin inhibitor with demonstrated in vitro and in vivo 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, P < 10(-7)) 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, P < 10(-6)). 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.

• Authors: T H T Nguyen, F Mentré, M Levi, J Yu, J Guedj
• Journal: Clinical pharmacology and therapeutics (Clin Pharmacol Ther) Vol. 96 Issue 5 Pg. 599-608 (Nov 2014) ISSN: 1532-6535 [Electronic] United States
• PMID: 25166216 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial)

Chemical References

• Antiviral Agents
• Cyclosporine
• Interferons
• alisporivir

Topics

• Antiviral Agents (pharmacokinetics)
• Cyclosporine (administration & dosage, pharmacokinetics, pharmacology)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (classification, drug effects)
• Hepatitis C (drug therapy, virology)
• Humans
• Interferons (administration & dosage)
• Male
• Models, Biological