Ke, Ruian; Loverdo, Claude; Qi, Hangfei; Olson, C Anders; Wu, Nicholas C; Sun, Ren; Lloyd-Smith, James O

doi:10.1093/jac/dkt423

Download PDF

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

2014

Published Web Location

https://doi.org/10.1093/jac/dkt423

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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content

For improved accessibility of PDF content, download the file to your device.

UCLA