Project description:This a model from the article:
Population-based analysis of methadone distribution and metabolism using an
age-dependent physiologically based pharmacokinetic model.
Yang F, Tong X, McCarver DG, Hines RN, Beard DA. J Pharmacokinet Pharmacodyn
2006 Aug;33(4):485-518 16758333
,
Abstract:
Limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to use
in methadone dosing recommendations in pediatric patients for either opioid
abstinence or analgesia. Considering the extreme inter-individual variability of
absorption and metabolism of methadone, population-based PK would be useful to
provide insight into the relationship between dose, blood concentrations, and
clinical effects of methadone. To address this need, an age-dependent
physiologically based pharmacokinetic (PBPK) model has been constructed to
systematically study methadone metabolism and PK. The model will facilitate the
design of cost-effective studies that will evaluate methadone PK and PD
relationships, and may be useful to guide methadone dosing in children. The PBPK
model, which includes whole-body multi-organ distribution, plasma protein
binding, metabolism, and clearance, is parameterized based on a database of
pediatric PK parameters and data collected from clinical experiments. The model
is further tailored and verified based on PK data from individual adults, then
scaled appropriately to apply to children aged 0-24 months. Based on measured
variability in CYP3A enzyme expression levels and plasma orosomucoid (ORM2)
concentrations, a Monte-Carlo-based simulation of methadone kinetics in a
pediatric population was performed. The simulation predicts extreme variability
in plasma concentrations and clearance kinetics for methadone in the pediatric
population, based on standard dosing protocols. In addition, it is shown that
when doses are designed for individuals based on prior protein expression
information, inter-individual variability in methadone kinetics may be greatly
reduced.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Yang F, Tong X, McCarver DG, Hines RN, Beard DA. (2006) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230040 | BioModels
Nick J. Plant 
