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Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification
In this paper we present a mathematical analysis of the basic model for target mediated drug disposition (TMDD). Assuming high affinity of ligand to target, we give a qualitative characterisation of ligand versus time graphs for different dosing regimes and derive accurate analytic approximations of...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446204/ https://www.ncbi.nlm.nih.gov/pubmed/22851162 http://dx.doi.org/10.1007/s10928-012-9260-6 |
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author | Peletier, Lambertus A. Gabrielsson, Johan |
author_facet | Peletier, Lambertus A. Gabrielsson, Johan |
author_sort | Peletier, Lambertus A. |
collection | PubMed |
description | In this paper we present a mathematical analysis of the basic model for target mediated drug disposition (TMDD). Assuming high affinity of ligand to target, we give a qualitative characterisation of ligand versus time graphs for different dosing regimes and derive accurate analytic approximations of different phases in the temporal behaviour of the system. These approximations are used to estimate model parameters, give analytical approximations of such quantities as area under the ligand curve and clearance. We formulate conditions under which a suitably chosen Michaelis–Menten model provides a good approximation of the full TMDD-model over a specified time interval. |
format | Online Article Text |
id | pubmed-3446204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-34462042012-09-26 Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification Peletier, Lambertus A. Gabrielsson, Johan J Pharmacokinet Pharmacodyn Original Paper In this paper we present a mathematical analysis of the basic model for target mediated drug disposition (TMDD). Assuming high affinity of ligand to target, we give a qualitative characterisation of ligand versus time graphs for different dosing regimes and derive accurate analytic approximations of different phases in the temporal behaviour of the system. These approximations are used to estimate model parameters, give analytical approximations of such quantities as area under the ligand curve and clearance. We formulate conditions under which a suitably chosen Michaelis–Menten model provides a good approximation of the full TMDD-model over a specified time interval. Springer US 2012-08-01 2012 /pmc/articles/PMC3446204/ /pubmed/22851162 http://dx.doi.org/10.1007/s10928-012-9260-6 Text en © The Author(s) 2012 https://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Paper Peletier, Lambertus A. Gabrielsson, Johan Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification |
title | Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification |
title_full | Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification |
title_fullStr | Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification |
title_full_unstemmed | Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification |
title_short | Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification |
title_sort | dynamics of target-mediated drug disposition: characteristic profiles and parameter identification |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446204/ https://www.ncbi.nlm.nih.gov/pubmed/22851162 http://dx.doi.org/10.1007/s10928-012-9260-6 |
work_keys_str_mv | AT peletierlambertusa dynamicsoftargetmediateddrugdispositioncharacteristicprofilesandparameteridentification AT gabrielssonjohan dynamicsoftargetmediateddrugdispositioncharacteristicprofilesandparameteridentification |