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

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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article numberdkt423
Pages (from-to)724-727
Number of pages4
JournalJournal of Antimicrobial Chemotherapy
Volume69
Issue number3
DOIs
StatePublished - Mar 2014
Externally publishedYes

Keywords

  • Hepatitis C virus
  • Mathematical modeling
  • Pharmacokinetics/pharmacodynamics
  • Resistance

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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