Repository Describing the Anatomical, Physiological, and Biological Changes in an Obese Population to Inform Physiologically Based Pharmacokinetic Models.

Berton, Mattia ORCID: 0000-0001-9450-2228, Bettonte, Sara ORCID: 0000-0002-7532-7898, Stader, Felix, Battegay, Manuel and Marzolini, Catia ORCID: 0000-0002-2312-7050 (2022) Repository Describing the Anatomical, Physiological, and Biological Changes in an Obese Population to Inform Physiologically Based Pharmacokinetic Models. Clinical pharmacokinetics, 61 (9). pp. 1251-1270.

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Official URL: http://dx.doi.org/10.1007/s40262-022-01132-3

Abstract

<h4>Background</h4>Obesity is associated with physiological changes that can affect drug pharmacokinetics. Obese individuals are underrepresented in clinical trials, leading to a lack of evidence-based dosing recommendations for many drugs. Physiologically based pharmacokinetic (PBPK) modelling can overcome this limitation but necessitates a detailed description of the population characteristics under investigation.<h4>Objective</h4>The purpose of this study was to develop and verify a repository of the current anatomical, physiological, and biological data of obese individuals, including population variability, to inform a PBPK framework.<h4>Methods</h4>A systematic literature search was performed to collate anatomical, physiological, and biological parameters for obese individuals. Multiple regression analyses were used to derive mathematical equations describing the continuous effect of body mass index (BMI) within the range 18.5-60 kg/m<sup>2</sup> on system parameters.<h4>Results</h4>In total, 209 studies were included in the database. The literature reported mostly BMI-related changes in organ weight, whereas data on blood flow and biological parameters (i.e. enzyme abundance) were sparse, and hence physiologically plausible assumptions were made when needed. The developed obese population was implemented in Matlab<sup>®</sup> and the predicted system parameters obtained from 1000 virtual individuals were in agreement with observed data from an independent validation obese population. Our analysis indicates that a threefold increase in BMI, from 20 to 60 kg/m<sup>2</sup>, leads to an increase in cardiac output (50%), liver weight (100%), kidney weight (60%), both the kidney and liver absolute blood flows (50%), and in total adipose blood flow (160%).<h4>Conclusion</h4>The developed repository provides an updated description of a population with a BMI from 18.5 to 60 kg/m<sup>2</sup> using continuous physiological changes and their variability for each system parameter. It is a tool that can be implemented in PBPK models to simulate drug pharmacokinetics in obese individuals.

Item Type:	Article
Uncontrolled Keywords:	Liver, Kidney, Humans, Obesity, Organ Size, Models, Biological
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	29 Feb 2024 09:20
Last Modified:	29 Feb 2024 09:20
DOI:	10.1007/s40262-022-01132-3
Open Access URL:	https://doi.org/10.1007/s40262-022-01132-3
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3178998