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

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.