Modelling clinical data shows active tissue concentration of daclatasvir is 10-fold lower than its plasma
Ruian Ke1, Claude Loverdo, Hangfei Qi
1Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA 90095, USA.
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.
Related Concept Videos
Volume of Distribution
Time Course of Drug Effect
Drug Distribution: Volume of Distribution
Drug Concentrations: Measurements
Plasma...
Drug Concentration Versus Time Correlation
Two pivotal parameters are the minimum effective concentration (MEC) and the minimum toxic concentration (MTC). The MEC is the...
Clearance Models: Compartment Models


