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.
Original language | English (US) |
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Article number | dkt423 |
Pages (from-to) | 724-727 |
Number of pages | 4 |
Journal | Journal of Antimicrobial Chemotherapy |
Volume | 69 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2014 |
Externally published | Yes |
Keywords
- Hepatitis C virus
- Mathematical modeling
- Pharmacokinetics/pharmacodynamics
- Resistance
ASJC Scopus subject areas
- Pharmacology
- Microbiology (medical)
- Pharmacology (medical)
- Infectious Diseases