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Clinical Pharmacokinetics
Erschienen in: Clinical Pharmacokinetics 4/2020

05.10.2019 | Original Research Article

Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population

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

Erschienen in: Clinical Pharmacokinetics | Ausgabe 4/2020

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Abstract

Background

Preterm neonates are usually not part of a traditional drug development programme, however they are frequently administered medicines. Developing modelling and simulation tools, such as physiologically based pharmacokinetic (PBPK) models that incorporate developmental physiology and maturation of drug metabolism, can be used to predict drug exposure in this group of patients, and may help to optimize drug dose adjustment.

Objective

The aim of this study was to assess and verify the predictability of a preterm PBPK model using compounds that undergo diverse renal and/or hepatic clearance based on the knowledge of their disposition in adults.

Methods

A PBPK model was developed in the Simcyp Simulator V17 to predict the pharmacokinetics (PK) of drugs in preterm neonates. Drug parameters for alfentanil, midazolam, caffeine, ibuprofen, gentamicin and vancomycin were collated from the literature. Predicted PK parameters and profiles were compared against the observed data.

Results

The preterm PBPK model predicted the PK changes of the six compounds using ontogeny functions for cytochrome P450 (CYP) 1A2, CYP2C9 and CYP3A4 after oral and intravenous administrations. For gentamicin and vancomycin, the maturation of renal function was able to predict the exposure of these two compounds after intravenous administration. All PK parameter predictions were within a twofold error criteria.

Conclusion

While the developed preterm model for the prediction of PK behaviour in preterm patients is not intended to replace clinical studies, it can potentially help with deciding on first-time dosing in this population and study design in the absence of clinical data.
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Metadaten
Titel
Preterm Physiologically Based Pharmacokinetic Model. Part II: Applications of the Model to Predict Drug Pharmacokinetics in the Preterm Population
verfasst von
Khaled Abduljalil
Xian Pan
Amita Pansari
Masoud Jamei
Trevor N. Johnson
Publikationsdatum
05.10.2019
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 4/2020
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-019-00827-4

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