A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics

Anissimov, YG and Roberts, MS (2002) A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics. Journal of Pharmacokinetics And Pharmacodynamics, 29 2: 131-156.


Author Anissimov, YG
Roberts, MS
Title A compartmental model of hepatic disposition kinetics: 1. Model development and application to linear kinetics
Journal name Journal of Pharmacokinetics And Pharmacodynamics   Check publisher's open access policy
ISSN 1567-567X
Publication date 2002
Sub-type Article (original research)
DOI 10.1023/A:1019703607647
Volume 29
Issue 2
Start page 131
End page 156
Total pages 26
Editor Thomas Ludden
Malcolm Rowland
Place of publication USA
Publisher Kluwer Academic/Plenum Publishers
Collection year 2002
Language eng
Subject C1
320501 Pharmaceutical Sciences and Pharmacy
730118 Organs, diseases and abnormal conditions not elsewhere classified
Abstract The conventional convection-dispersion model is widely used to interrelate hepatic availability (F) and clearance (Cl) with the morphology and physiology of the liver and to predict effects such as changes in liver blood flow on F and Cl. The extension of this model to include nonlinear kinetics and zonal heterogeneity of the liver is not straightforward and requires numerical solution of partial differential equation, which is not available in standard nonlinear regression analysis software. In this paper, we describe an alternative compartmental model representation of hepatic disposition (including elimination). The model allows the use of standard software for data analysis and accurately describes the outflow concentration-time profile for a vascular marker after bolus injection into the liver. In an evaluation of a number of different compartmental models, the most accurate model required eight vascular compartments, two of them with back mixing. In addition, the model includes two adjacent secondary vascular compartments to describe the tail section of the concentration-time profile for a reference marker. The model has the added flexibility of being easy to modify to model various enzyme distributions and nonlinear elimination. Model predictions of F, MTT, CV2, and concentration-time profile as well as parameter estimates for experimental data of an eliminated solute (palmitate) are comparable to those for the extended convection-dispersion model.
Keyword Pharmacology & Pharmacy
Compartmental Model
Dispersion Model
Hepatic Elimination
Inverse Gaussian Distribution
Secondary Vascular Compartment
Hepatic Disposition
Perfused Rat-liver
Multiple-indicator Dilution
Convection-dispersion Model
Organ Distribution Kinetics
Interconnected-tubes Model
Transit-time
Local Pharmacokinetics
Boundary-conditions
Salicylic-acid
Elimination
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
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