A Systematic Review of Published Physiologically-based Kinetic Models and an Assessment of their Chemical Space Coverage

Thompson, Courtney V, Firman, James W, Goldsmith, Michael R, Grulke, Christopher M, Tan, Yu-Mei, Paini, Alicia, Penson, Peter E ORCID: 0000-0001-6763-1489, Sayre, Risa R, Webb, Steven and Madden, Judith C (2021) A Systematic Review of Published Physiologically-based Kinetic Models and an Assessment of their Chemical Space Coverage. ATLA-ALTERNATIVES TO LABORATORY ANIMALS, 49 (5). pp. 197-208.

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Official URL: http://dx.doi.org/10.1177/02611929211060264

Abstract

Across multiple sectors, including food, cosmetics and pharmaceutical industries, there is a need to predict the potential effects of xenobiotics. These effects are determined by the intrinsic ability of the substance, or its derivatives, to interact with the biological system, and its concentration-time profile at the target site. Physiologically-based kinetic (PBK) models can predict organ-level concentration-time profiles, however, the models are time and resource intensive to generate <i>de novo</i>. Read-across is an approach used to reduce or replace animal testing, wherein information from a data-rich chemical is used to make predictions for a data-poor chemical. The recent increase in published PBK models presents the opportunity to use a read-across approach for PBK modelling, that is, to use PBK model information from one chemical to inform the development or evaluation of a PBK model for a similar chemical. Essential to this process, is identifying the chemicals for which a PBK model already exists. Herein, the results of a systematic review of existing PBK models, compliant with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) format, are presented. Model information, including species, sex, life-stage, route of administration, software platform used and the availability of model equations, was captured for 7541 PBK models. Chemical information (identifiers and physico-chemical properties) has also been recorded for 1150 unique chemicals associated with these models. This PBK model data set has been made readily accessible, as a Microsoft Excel<sup>®</sup> spreadsheet, providing a valuable resource for those developing, using or evaluating PBK models in industry, academia and the regulatory sectors.

Item Type:	Article
Uncontrolled Keywords:	PBK, PBPK, PBTK, systematic review, pharmacokinetic modelling, read-across
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	05 May 2022 14:57
Last Modified:	18 Jan 2023 21:04
DOI:	10.1177/02611929211060264
Open Access URL:	https://journals.sagepub.com/doi/10.1177/026119292...
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3154335