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Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Blood Components and Binding Proteins

Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Blood Components... BackgroundFetal blood and plasma volume and binding components are critical parameters in a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of their changes during fetal development has not been reported.ObjectiveThe objective of this work was to collate and analyze physiological information on fetal blood and plasma volume and binding component data during development and to provide a mathematical description of these parameters that can be integrated within a fetal physiologically based pharmacokinetic model.MethodsA comprehensive literature search was conducted on fetal blood and plasma volume and binding component parameters and their changes during growth from apparently healthy fetuses from uncomplicated pregnancies. Collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing their growth trends with fetal age and weight.ResultsData were available from 14 studies for blood, ten studies for hematocrit, 12 studies for albumin, and four studies for alpha-1-acid glycoprotein, while plasma and red blood cell volumes were described based on blood and hematocrit data. Fetal physiologically based pharmacokinetic parameters, including blood, plasma and red blood cell volumes, hematocrit, serum albumin, and acid glycoprotein were quantified as a function of fetal age and weight. Variability around the mean parameters at different fetal ages was also investigated. The growth of each of these parameters was different (with respect to direction and monotonicity).ConclusionsDespite the limitations identified in the availability of some values, the collected data presented in this article provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications include predicting xenobiotic exposure and risk assessment in the fetus following maternally administered drugs or unintended exposure to environmental toxicants. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Pharmacokinetics Springer Journals

Fetal Physiologically Based Pharmacokinetic Models: Systems Information on Fetal Blood Components and Binding Proteins

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References (94)

Publisher
Springer Journals
Copyright
Copyright © Springer Nature Switzerland AG 2019
Subject
Medicine & Public Health; Pharmacotherapy; Pharmacology/Toxicology; Internal Medicine
ISSN
0312-5963
eISSN
1179-1926
DOI
10.1007/s40262-019-00836-3
Publisher site
See Article on Publisher Site

Abstract

BackgroundFetal blood and plasma volume and binding components are critical parameters in a fetal physiologically based pharmacokinetic model. To date, a comprehensive review of their changes during fetal development has not been reported.ObjectiveThe objective of this work was to collate and analyze physiological information on fetal blood and plasma volume and binding component data during development and to provide a mathematical description of these parameters that can be integrated within a fetal physiologically based pharmacokinetic model.MethodsA comprehensive literature search was conducted on fetal blood and plasma volume and binding component parameters and their changes during growth from apparently healthy fetuses from uncomplicated pregnancies. Collated data were assessed, integrated, and analyzed to establish continuous mathematical functions describing their growth trends with fetal age and weight.ResultsData were available from 14 studies for blood, ten studies for hematocrit, 12 studies for albumin, and four studies for alpha-1-acid glycoprotein, while plasma and red blood cell volumes were described based on blood and hematocrit data. Fetal physiologically based pharmacokinetic parameters, including blood, plasma and red blood cell volumes, hematocrit, serum albumin, and acid glycoprotein were quantified as a function of fetal age and weight. Variability around the mean parameters at different fetal ages was also investigated. The growth of each of these parameters was different (with respect to direction and monotonicity).ConclusionsDespite the limitations identified in the availability of some values, the collected data presented in this article provide a useful resource for fetal physiologically based pharmacokinetic modeling. Potential applications include predicting xenobiotic exposure and risk assessment in the fetus following maternally administered drugs or unintended exposure to environmental toxicants.

Journal

Clinical Pharmacokinetics – Springer Journals

Published: May 7, 2020

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