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 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.
Evans
N D
ND
School of Engineering, University of Warwick, Coventry CV4 7AL, England.
Godfrey
K R
KR
Chapman
M J
MJ
Chappell
M J
MJ
Aarons
L
L
Duffull
S B
SB
D000284:Administration, Oral; D001552:Benzazepines / Q000378:metabolism / Q000493:pharmacokinetics*; D001711:Biotransformation; D001825:Body Fluid Compartments; D002316:Cardiotonic Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D000077550:Ivabradine; D008432:Mathematical Computing; D008954:Models, Biological
D001552:Benzazepines; D002316:Cardiotonic Agents; C413689:S 18982; D000077550:Ivabradine