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Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration

Ke, R and Loverdo, C and Qi, H and Olson, CA and Wu, NC and Sun, R and Lloyd-Smith, JO (2014) Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration. Journal of Antimicrobial Chemotherapy. pp. 724-727.

Abstract

Objectives: Daclatasvir is a highly potent inhibitor of hepatitis C virus. We estimated the active tissue concentration of daclatasvir in vivo. Methods: We developed a mathematical model incorporating pharmacokinetic/pharmacodynamic and viral dynamics. By fitting the model to clinical data reported previously, we estimated the ratio between plasma drug concentration and active tissue concentration in vivo. Results: The modelling results show that the active tissue concentration of daclatasvir is ~9% of the concentration measured in plasma (95% CI 1%=29%). Conclusions: Using plasma concentrations as surrogates for clinical recommendations may lead to substantial underestimation of the risk of resistance. The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Item Type: Article
Additional Information: NIBR author: Sun, R institute: NIBR contributor address: (Ke, Loverdo, Lloyd-smith) Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, United States (Qi, Olson, Sun) Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, United States (Wu) The Molecular Biology Institute, University of California, Los Angeles, CA 90095, United States (Sun) Department of Infectious Diseases, Novartis Institutes for BioMedical Research, Emeryville, CA 94608, United States (Lloyd-smith) Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, United States
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22606

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