article · 01/03/2014
Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration
Résumé
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 similar to 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.
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Ke, R., Loverdo, C., Qi, H., Olson, C.-A., Wu, N.-C., Sun, R., & Lloyd-Smith, J.-O. (2014). Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration. J. Antimicrob. Chemother., 69(3). https://doi.org/10.1093/jac/dkt423@article{Ke2014_300,
author = {Ke, Ruian and Loverdo, Claude and Qi, Hangfei and Olson, C. Anders and Wu, Nicholas C. and Sun, Ren and Lloyd-Smith, James O.},
year = {2014},
month = {3},
title = {Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration},
journal = {J. Antimicrob. Chemother.},
publisher = {OXFORD UNIV PRESS},
volume = {69},
number = {3},
address = {GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND},
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 similar to 9\textbackslash{}\% of the concentration measured in plasma (95\textbackslash{}\% CI 1\textbackslash{}\%-29\textbackslash{}\%). Conclusions: Using plasma concentrations as surrogates for clinical recommendations may lead to substantial underestimation of the risk of resistance.},
url = {http://www.dx.doi.org/10.1093/jac/dkt423},
doi = {10.1093/jac/dkt423},
issn = {0305-7453},
}TY - JOUR
AU - Ke, Ruian
AU - Loverdo, Claude
AU - Qi, Hangfei
AU - Olson, C. Anders
AU - Wu, Nicholas C.
AU - Sun, Ren
AU - Lloyd-Smith, James O.
PY - 2014
DA - 2014/03/01
TI - Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma concentration
JO - J. Antimicrob. Chemother.
VL - 69
IS - 3
PB - OXFORD UNIV PRESS
SN - 0305-7453
AB - 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 similar to 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.
DO - 10.1093/jac/dkt423
UR - http://www.dx.doi.org/10.1093/jac/dkt423
ER -