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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...

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Detalles Bibliográficos
Autores principales: Peletier, Lambertus A., Gabrielsson, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2012
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.
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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
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