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.
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.
Entities:
Keywords:
hepatitis C virus; mathematical modeling; pharmacokinetics/pharmacodynamics; resistance
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