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Physiologically Based Pharmacokinetic Modelling in Drug Discovery and Clinical Development: A Treatise on Concepts, Model Workflow, Credibility, Application and Regulatory Landscape

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Abstract

Physiologically based pharmacokinetic modelling (PBPK) approach considers the body as a multi-compartment system where physiological organs and kinetics of drug transfer between them are modelled using mathematical expressions. It is a mechanistic approach capable of handling complex clinical scenarios, fast gaining regulatory acceptance for the potential to predict PK during drug discovery and development in a target population of interest. Recently PBPK has been used to answer various clinical pharmacology questions related to drug-drug interactions (DDIs), food effects, formulation effects, PK in organ impaired populations and specific populations like paediatrics and pregnancy. This chapter describes the basics of PBPK modelling for small and large molecule drugs, its role/engagement during different stages of discovery, preclinical and clinical development, approaches to construct and assess the credibility of the model, applications in clinical development pharmacology, regulatory guidance, potential challenges, and future developments in the area of PBPK modelling.

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Correspondence to Pradeep Sharma .

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Pradeep Sharma, Jin Dong, Vijender Panduga and David W Boulton are employees and/or shareholders of AstraZeneca, and Felix Stader is an employee of Simcyp Division (Certara UK Limited). Simcyp® is a proprietary PBPK modelling software platform of the Simcyp division of Certara UK Ltd.

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Sharma, P., Stader, F., Panduga, V., Dong, J., Boulton, D.W. (2023). Physiologically Based Pharmacokinetic Modelling in Drug Discovery and Clinical Development: A Treatise on Concepts, Model Workflow, Credibility, Application and Regulatory Landscape. In: Jagadeesh, G., Balakumar, P., Senatore, F. (eds) The Quintessence of Basic and Clinical Research and Scientific Publishing. Springer, Singapore. https://doi.org/10.1007/978-981-99-1284-1_16

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