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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 4/2020

01-04-2020 | Original Research Article

A Preterm Physiologically Based Pharmacokinetic Model. Part I: Physiological Parameters and Model Building

Authors: Khaled Abduljalil, Xian Pan, Amita Pansari, Masoud Jamei, Trevor N. Johnson

Published in: Clinical Pharmacokinetics | Issue 4/2020

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Abstract

Background

Developmental physiology can alter pharmacotherapy in preterm populations. Because of ethical and clinical constraints in studying this vulnerable age group, physiologically based pharmacokinetic models offer a viable alternative approach to predicting drug pharmacokinetics and pharmacodynamics in this population. However, such models require comprehensive information on the changes of anatomical, physiological and biochemical variables, where such data are not available in a single source.

Objective

The objective of this study was to integrate the relevant physiological parameters required to build a physiologically based pharmacokinetic model for the preterm population.

Methods

Published information on developmental preterm physiology and some drug-metabolising enzymes were collated and analysed. Equations were generated to describe the changes in parameter values during growth.

Results

Data on organ size show different growth patterns that were quantified as functions of bodyweight to retain physiological variability and correlation. Protein binding data were quantified as functions of age as the body weight was not reported in the original articles. Ontogeny functions were derived for cytochrome P450 1A2, 3A4 and 2C9. Tissue composition values and how they change with age are limited.

Conclusions

Despite the limitations identified in the availability of some tissue composition values, the data presented in this article provide an integrated resource of system parameters needed for building a preterm physiologically based pharmacokinetic model.
Appendix
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Metadata
Title
A Preterm Physiologically Based Pharmacokinetic Model. Part I: Physiological Parameters and Model Building
Authors
Khaled Abduljalil
Xian Pan
Amita Pansari
Masoud Jamei
Trevor N. Johnson
Publication date
01-04-2020
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 4/2020
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00825-6

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