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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 11/2019

Open Access 01-11-2019 | Current Opinion

Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) Models and Overcoming Some of the Challenges to Meeting Them

Authors: Sheila Annie Peters, Hugues Dolgos

Published in: Clinical Pharmacokinetics | Issue 11/2019

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Abstract

When scientifically well-founded, the mechanistic basis of physiologically based pharmacokinetic (PBPK) models can help reduce the uncertainty and increase confidence in extrapolations outside the studied scenarios or studied populations. However, it is not always possible to establish mechanistically credible PBPK models. Requirements to establishing confidence in PBPK models, and challenges to meeting these requirements, are presented in this article. Parameter non-identifiability is the most challenging among the barriers to establishing confidence in PBPK models. Using case examples of small molecule drugs, this article examines the use of hypothesis testing to overcome parameter non-identifiability issues, with the objective of enhancing confidence in the mechanistic basis of PBPK models and thereby improving the quality of predictions that are meant for internal decisions and regulatory submissions. When the mechanistic basis of a PBPK model cannot be established, we propose the use of simpler models or evidence-based approaches.
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Metadata
Title
Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) Models and Overcoming Some of the Challenges to Meeting Them
Authors
Sheila Annie Peters
Hugues Dolgos
Publication date
01-11-2019
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 11/2019
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00790-0

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