In silico evaluation of warfarin–bucolome therapy

Research output: Contribution to journalArticle

Abstract

Purpose: Some reports have suggested that bucolome, an inhibitor of cytochrome P450 2C9, is useful for decreasing inter-patient variation in warfarin clearance. The purpose of the present study was to evaluate the utility of the concomitant administration of bucolome and warfarin using an in silico approach. Methods: In vitro data regarding the enzymatic kinetics of (S)-warfarin and bucolome were collected from the literature. As a validation study, the geometric mean (GM) of the oral unbound clearance of (S)-warfarin and its inter-patient variation (assessed using the standard deviation of its natural logarithm (σ)) were predicted using a physiologically based population pharmacokinetic simulator (SimcypTM) and compared with clinical data. The utility of the concomitant administration was evaluated by comparing the GM and σ values predicted under various conditions (the prediction study). Results and Discussion: The σ values in the presence and absence of bucolome were predicted to be 0.73 and 0.68, respectively, suggesting that bucolome might increase the inter-patient variation, as clinically observed. In the prediction study, the σ value of the bucolome co-administered group was greater in almost all of the examined conditions. In conclusion, the concomitant administration of bucolome might not be useful for reducing the inter-patient variation of (S)-warfarin pharmacokinetics.

Original languageEnglish
Pages (from-to)233-242
Number of pages10
JournalBiopharmaceutics and Drug Disposition
DOIs
Publication statusPublished - 2016

    Fingerprint

Keywords

  • bucolomel
  • CYP2C9
  • DDI
  • warfarin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this