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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 6/2019

Open Access 01-06-2019 | Review Article

Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies

Authors: Neil A. Miller, Micaela B. Reddy, Aki T. Heikkinen, Viera Lukacova, Neil Parrott

Published in: Clinical Pharmacokinetics | Issue 6/2019

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Abstract

Physiologically based pharmacokinetic modelling is well established in the pharmaceutical industry and is accepted by regulatory agencies for the prediction of drug–drug interactions. However, physiologically based pharmacokinetic modelling is valuable to address a much wider range of pharmaceutical applications, and new regulatory impact is expected as its full power is leveraged. As one example, physiologically based pharmacokinetic modelling is already routinely used during drug discovery for in-vitro to in-vivo translation and pharmacokinetic modelling in preclinical species, and this leads to the application of verified models for first-in-human pharmacokinetic predictions. A consistent cross-industry strategy in this application area would increase confidence in the approach and facilitate further learning. With this in mind, this article aims to enhance a previously published first-in-human physiologically based pharmacokinetic model-building strategy. Based on the experience of scientists from multiple companies participating in the GastroPlus™ User Group Steering Committee, new Absorption, Distribution, Metabolism and Excretion knowledge is integrated and decision trees proposed for each essential component of a first-in-human prediction. We have reviewed many relevant scientific publications to identify new findings and highlight gaps that need to be addressed. Finally, four industry case studies for more challenging compounds illustrate and highlight key components of the strategy.
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Metadata
Title
Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies
Authors
Neil A. Miller
Micaela B. Reddy
Aki T. Heikkinen
Viera Lukacova
Neil Parrott
Publication date
01-06-2019
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 6/2019
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00741-9

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