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Clinical Pharmacokinetics

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14-11-2023 | Cefuroxime | Original Research Article

Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime

Authors: Xiaomei I. Liu, Dionna J. Green, John van den Anker, Homa K. Ahmadzia, Gilbert J. Burckart, André Dallmann

Published in: Clinical Pharmacokinetics | Issue 1/2024

Abstract

Background and Objective

Physiologically based pharmacokinetic (PBPK) models for pregnant women have recently been successfully used to predict maternal and umbilical cord pharmacokinetics (PK). Because there is very limited opportunity for conducting clinical and PK investigations for fetal drug exposure, PBPK models may provide further insights. The objectives of this study were to extend a whole-body pregnancy PBPK model by multiple compartments representing fetal organs, and to predict the PK of cefuroxime in the maternal and fetal plasma, the amniotic fluid, and several fetal organs.

Methods

To this end, a previously developed pregnancy PBPK model for cefuroxime was updated using the open-source software Open Systems Pharmacology (PK-Sim^®/MoBi^®). Multiple compartments were implemented to represent fetal organs including brain, heart, liver, lungs, kidneys, the gastrointestinal tract (GI), muscles, and fat tissue, as well as another compartment lumping organs and tissues not explicitly represented.

Results

This novel PBPK model successfully predicted cefuroxime concentrations in maternal blood, umbilical cord, amniotic fluid, and several fetal organs including heart, liver, and lungs. Further model validation with additional clinical PK data is needed to build confidence in the model.

Conclusions

Being developed with an open-source software, the presented generic model can be freely re-used and tailored to address specific questions at hand, e.g., to assist the design of clinical studies in the context of drug research or to predict fetal organ concentrations of chemicals in the context of fetal health risk assessment.

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Title: Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime
Authors: Xiaomei I. Liu
Dionna J. Green
John van den Anker
Homa K. Ahmadzia
Gilbert J. Burckart
André Dallmann
Publication date: 14-11-2023
Publisher: Springer International Publishing
Keywords: Cefuroxime
Pharmacokinetics
Published in: Clinical Pharmacokinetics / Issue 1/2024
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-023-01323-6

At a glance: The STEP trials

Springer Medicine

Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime

Abstract

Background and Objective

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background and Objective

Methods

Results

Conclusions

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