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

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...

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Bibliographic Details
Published in:Journal of pharmacokinetics and pharmacodynamics 2001-02, Vol.28 (1), p.93-105
Main Authors: Evans, N D, Godfrey, K R, Chapman, M J, Chappell, M J, Aarons, L, Duffull, S B
Format: Article
Language:English
Subjects:
Administration, Oral
Benzazepines - metabolism
Benzazepines - pharmacokinetics
Biotransformation
Body Fluid Compartments
Cardiotonic Agents - metabolism
Cardiotonic Agents - pharmacokinetics
Injections, Intravenous
Mathematical Computing
Models, Biological
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Summary: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.
ISSN:1567-567X
1573-8744
DOI:10.1023/A:1011521819898