- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2007-06-17 23:43:10+12:00
- Desc:
- committing version01 of yang_tong_mccarver_hines_beard_2006
- Permanent Source URI:
- http://models.cellml.org/workspace/yang_tong_mccarver_hines_beard_2006/rawfile/023dc90f2bca9fe21401ad23f3fa5fb50b2ab5ae/yang_tong_mccarver_hines_beard_2006.cellml
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<!-- FILE : yang_model_2006_version01.xml
CREATED : 5th June 2007
LAST MODIFIED : 5th June 2007
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.1 Specification.
DESCRIPTION : This file contains a CellML description of Yang et al.'s
age-dependent, physiologically based pharmokinetic model of methadone distribution and metabolism.
CHANGES:
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<article>
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<title>An Age-Dependent Physiologically Based Pharmokinetic Model of Methadone Distribution and Metabolism</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Methadone is a synthetic analgesic (painkiller) which is commonly given to both adults and children. Although methadone is commonly administered to children, the majority of the studies on methadone pharmacokinetics (PK) and pharmacodynamics (PD) have been carried out on adults. Once it has been absorbed into the systemic circulation, methadone is distributed to the brain, lungs, kidneys, muscle, liver, and intestine and it is principally metabolised in the latter two sites.
</para>
<para>
In the publication described here, Yang <emphasis>et al.</emphasis> develop a physiologically-based pharmacokinetic (PBPK) model specifically for infants aged 0-24 months old. The PBPK model includes whole body, multi-organ distribution (see the figure below), plasma protein binding, metabolism, and clearance, and its parameters are based on a database of pediatric pharmacokinetics parameters and data collected from clinical experiments. The model is further supported by data from individual adults, and is then scaled to be suitable for children aged 0-24 months old.
</para>
<para>
The model simulations predict there are large variations in plasma concentrations and clearance kinetics for methadone amongst children.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.springerlink.com/content/9vr1m44700771013/">Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model</ulink>, Feng Yang, Xianping Tong, D. Gail. McCarver, Ronald N. Hines and Daniel A. Beard, 2006, <ulink url="http://www.springerlink.com/content/105728/">
<emphasis>Journal of Pharmacokinetics and Pharmacodynamics</emphasis>
</ulink>, volume 33, issue 4. (a <ulink url="http://www.springerlink.com/content/9vr1m44700771013/fulltext.pdf">PDF</ulink> versions of the article are available on the <emphasis>Journal of Pharmacokinetics and Pharmacodynamics</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/sites/entrez?Db=PubMed&Cmd=ShowDetailView&TermToSearch=16758333&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum">PubMed ID: 16758333</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
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<title>model diagram</title>
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<caption>Schematic diagram of a PBPK model consisting of 17 compartments. The lines represent blood flow while the boxes represent organs or systems. Methadone is primarily metabolised in the liver and gastro-intestinal (GI) system, while its elimination mainly occurs through the kidneys. Organs in which methadone are not distributed include skin, adipose, thyroid, pancreas, and bone marrow are grouped together as <emphasis>others</emphasis>.</caption>
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Yang et al.'s age-dependent, physiologically based pharmokinetic model of methadone distribution and metabolism.
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This is the CellML description of Yang et al.'s age-dependent, physiologically based pharmokinetic model of methadone distribution and metabolism. In this particular example of the model, the liver has been chosen to represent the organ k, and therefore all the parameter values are specific for this organ. Further, the model has been focused on a 5 year old child.
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Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model
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Population-based analysis of methadone distribution and metabolism using an age-dependent physiologically based pharmacokinetic model
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Yang et al.'s age-dependent, physiologically based pharmokinetic model of methadone distribution and metabolism.
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