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

Nguyen, TH and Mentre, F and Levi, M and Yu, J and Guedj, J (2014) A pharmacokinetic - viral kinetic model describes the effect of alisporivir monotherapy or in combination with peg-IFN on hepatitis C virologic response. Clinical Pharmacology and Therapeutics.

Abstract

Alisporivir is a cyclophilin inhibitor with demonstrated in vitro and in vivo activity against hepatitis C virus (HCV). We estimated antiviral effectiveness of alisporivir alone or in combination with pegylated-Inteferon (peg-IFN) in 88 patients infected with different HCV genotypes treated for four weeks. The pharmacokinetics of both drugs were modeled and used as driving functions for the viral kinetic model. Genotype was found to significantly affect pegylated-Inteferon effectiveness (varepsilon= 86.3% and 99.1% in genotype-1/4 and genotype-2/3, respectively, p<10-7) and infected cells loss rate (delta= 0.22 vs 0.39 day-1 in genotype-1/4 and genotype-2/3, respectively, p<10-6). Alisporivir effectiveness was not significantly different across genotype and was high for doses >/=600 mg QD. 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 optimize alisporivir-based therapies.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 28 August 2014; doi:10.1038/clpt.2014.173

Item Type: Article
Additional Information: NIBR author: Yu, J institute: NIBR contributor address:
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/23442

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