An identifiability analysis of a parent-metabolite pharmacokinetic model for ivabradine

J Pharmacokinet Pharmacodyn. 2001 Feb;28(1):93-105. doi: 10.1023/a:1011521819898.

Abstract

The paper considers the structural identifiability of a parent-metabolite pharmacokinetic model for ivabradine and one of its metabolites. The model, which is linear, is considered initially for intravenous administration of ivabradine, and then for a combined intravenous and oral administration. In both cases, the model is shown to be unidentifiable. Simplification of the model (for both forms of administration) to that proposed by Duffull et al. (1) results in a globally structurally identifiable model. The analysis could be applied to the modeling of any drug undergoing first-pass metabolism, with plasma concentrations available from drug and metabolite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Benzazepines / metabolism
  • Benzazepines / pharmacokinetics*
  • Biotransformation
  • Body Fluid Compartments
  • Cardiotonic Agents / metabolism
  • Cardiotonic Agents / pharmacokinetics*
  • Injections, Intravenous
  • Ivabradine
  • Mathematical Computing
  • Models, Biological*

Substances

  • Benzazepines
  • Cardiotonic Agents
  • S 18982
  • Ivabradine