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An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models

Mathematical models are routinely used in clinical pharmacology to study the pharmacokinetic and pharmacodynamic properties of a drug in the body. Identifiability of these models is an important requirement for the success of these clinical studies. Identifiability is classified into two types, stru...

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Detalles Bibliográficos
Autores principales: Shivva, V, Korell, J, Tucker, I G, Duffull, S B
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697038/
https://www.ncbi.nlm.nih.gov/pubmed/23887745
http://dx.doi.org/10.1038/psp.2013.25
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author Shivva, V
Korell, J
Tucker, I G
Duffull, S B
author_facet Shivva, V
Korell, J
Tucker, I G
Duffull, S B
author_sort Shivva, V
collection PubMed
description Mathematical models are routinely used in clinical pharmacology to study the pharmacokinetic and pharmacodynamic properties of a drug in the body. Identifiability of these models is an important requirement for the success of these clinical studies. Identifiability is classified into two types, structural identifiability related to the structure of the mathematical model and deterministic identifiability which is related to the study design. There are existing approaches for assessment of structural identifiability of fixed-effects models, although their use appears uncommon in the literature. In this study, we develop an informal unified approach for simultaneous assessment of structural and deterministic identifiability for fixed and mixed-effects pharmacokinetic or pharmacokinetic–pharmacodynamic models. This approach uses an information theoretic framework. The method is applied both to simple examples to explore known identifiability properties and to a more complex example to illustrate its utility.
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spelling pubmed-36970382013-07-01 An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models Shivva, V Korell, J Tucker, I G Duffull, S B CPT Pharmacometrics Syst Pharmacol Original Article Mathematical models are routinely used in clinical pharmacology to study the pharmacokinetic and pharmacodynamic properties of a drug in the body. Identifiability of these models is an important requirement for the success of these clinical studies. Identifiability is classified into two types, structural identifiability related to the structure of the mathematical model and deterministic identifiability which is related to the study design. There are existing approaches for assessment of structural identifiability of fixed-effects models, although their use appears uncommon in the literature. In this study, we develop an informal unified approach for simultaneous assessment of structural and deterministic identifiability for fixed and mixed-effects pharmacokinetic or pharmacokinetic–pharmacodynamic models. This approach uses an information theoretic framework. The method is applied both to simple examples to explore known identifiability properties and to a more complex example to illustrate its utility. Nature Publishing Group 2013-06 2013-06-19 /pmc/articles/PMC3697038/ /pubmed/23887745 http://dx.doi.org/10.1038/psp.2013.25 Text en Copyright © 2013 American Society for Clinical Pharmacology and Therapeutics http://creativecommons.org/licenses/by-nc-nd/3.0/ CPT: Pharmacometrics and Systems Pharmacology is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
spellingShingle Original Article
Shivva, V
Korell, J
Tucker, I G
Duffull, S B
An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models
title An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models
title_full An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models
title_fullStr An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models
title_full_unstemmed An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models
title_short An Approach for Identifiability of Population Pharmacokinetic–Pharmacodynamic Models
title_sort approach for identifiability of population pharmacokinetic–pharmacodynamic models
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697038/
https://www.ncbi.nlm.nih.gov/pubmed/23887745
http://dx.doi.org/10.1038/psp.2013.25
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