A pharmacokinetic simulation model for ivabradine in healthy volunteers

Research output: Contribution to journalArticle

  • External authors:
  • Stephen B. Duffull
  • Sylvie Chabaud
  • Patrice Nony
  • Christian Laveille
  • Pascal Girard


Ivabradine is a novel bradycardic agent that has been developed for the prevention of angina. Ivabradine has an active metabolite S-18982. The aim of this study is to develop a pharmacokinetic simulation model. Pharmacokinetic data from two studies were pooled and included data from a total of 66 healthy male volunteers. The data were collected following single dose intravenous and multiple dose oral administration of ivabradine. The multiple dose regimens were administered every 12 h and there were seven active dosing levels. The modelling was performed using the NONMEM software. The model was assessed in terms of its ability to describe the original data set used in its construction and also data arising from a different clinical pharmacology study involving 12 additional subjects. The pharmacokinetics of ivabradine and S-18982 were best described by two linked two compartment intravenous bolus and first-order input, with first-pass loss, and first-order output model. When the model was used for simulation it produced an adequate description of both the original data and data arising from a different clinical pharmacology study. (C) 2000 Elsevier Science B.V.

Bibliographical metadata

Original languageEnglish
Pages (from-to)285-294
Number of pages9
JournalEuropean Journal of Pharmaceutical Sciences
Issue number4
Publication statusPublished - Jun 2000