A pharmacokinetic simulation model for ivabradine in healthy volunteers

Eur J Pharm Sci. 2000;10(4):285-94. doi: 10.1016/s0928-0987(00)00086-5.


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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzazepines / administration & dosage
  • Benzazepines / blood
  • Benzazepines / pharmacokinetics*
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / blood
  • Cardiotonic Agents / pharmacokinetics*
  • Humans
  • Ivabradine
  • Male
  • Models, Biological*


  • Benzazepines
  • Cardiotonic Agents
  • S 18982
  • Ivabradine