- Author:
- Hanne <Hanne@hanne-nielsens-macbook.local>
- Date:
- 2009-10-27 11:38:28+13:00
- Desc:
- Added images in ai png and svg format
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/grange_2001/rawfile/abbc4671930b2f516bd9bf82a537c0455b3d8cfe/grange_holford_guentert_2001_noncompartmental.cellml
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This CellML file was generated on 20/10/2009 at 9:43:32 at a.m. using:
COR (0.9.31.1319)
Copyright 2002-2009 Dr Alan Garny
http://cor.physiol.ox.ac.uk/ - cor@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.cellml.org/
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<title>A pharmacokinetic model to predict the PK interaction of L-dopa and benserazide in rats.
</title>
<author>
<firstname>Geoffrey</firstname>
<surname>Nunns</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in PCenv, COR and OpenCell to recreate the published results (Figure 6). This model only describes the non-compartmental model of L-dopa handling, and does not adress benserazide metabolism.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
PURPOSE: To study the PK interaction of L-dopa/benserazide in rats. METHODS: Male rats received a single oral dose of 80 mg/kg L-dopa or 20 mg/kg benserazide or 80/20 mg/kg L-dopa/benserazide. Based on plasma concentrations the kinetics of L-dopa, 3-O-methyldopa (3-OMD), benserazide, and its metabolite Ro 04-5127 were characterized by noncompartmental analysis and a compartmental model where total L-dopa clearance was the sum of the clearances mediated by amino-acid-decarboxylase (AADC), catechol-O-methyltransferase and other enzymes. In the model Ro 04-5127 inhibited competitively the L-dopa clearance by AADC. RESULTS: The coadministration of L-dopa/benserazide resulted in a major increase in systemic exposure to L-dopa and 3-OMD and a decrease in L-dopa clearance. The compartmental model allowed an adequate description of the observed L-dopa and 3-OMD concentrations in the absence and presence of benserazide. It had an advantage over noncompartmental analysis because it could describe the temporal change of inhibition and recovery of AADC. CONCLUSIONS: Our study is the first investigation where the kinetics of benserazide and Ro 04-5127 have been described by a compartmental model. The L-dopa/benserazide model allowed a mechanism-based view of the L-dopa/benserazide interaction and supports the hypothesis that Ro 04-5127 is the primary active metabolite of benserazide.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
A pharmacokinetic model to predict the PK interaction of L-dopa and benserazide in rats, Susan Grange, Nicholas H. G. Holford, Theodor W. Guentert, 2001, <emphasis>Pharm Res.</emphasis>, volume 18, 1174-1184. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11587490 &query_hl=1&itool=pubmed_docsum">PubMed ID: 11587490 </ulink>
</para>
</sect1>
</article>
</documentation>
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