Development, Early Verification and Application of a North American Pediatric PBPK Model, Comparison With the North European Pediatric Population
4 affiliations
- 1Certara Predictive Technologies Sheffield UK
- 2Mathematical Sciences University of Malawi Zomba Malawi
- 3Division of Population Health, School of Health Sciences, Centre for Biostatistics University of Manchester Manchester UK
- 4Department of Pharmacy, Pharmacology and Toxicology Radboud University Medical Center Nijmegen the Netherlands
Abstract
Physiologically based pharmacokinetic (PBPK) models are increasingly used in pediatric drug development and matching such models to the target population is an important consideration. A US pediatric PBPK model was developed incorporating four sub‐groups describing physiology and enzymatic/transporter levels for White, African American, Hispanic/Latino and Asian subjects. Virtual populations could then be created reflecting the demographics of the clinical study design. Ten different drugs (14 studies) were used to verify the pediatric PBPK model performance. Predicted PK parameters showed reasonable agreement with observed data, 50% of the predicted: observed values were within 0.8–1.25‐fold, 74% within 0.67–1.5‐fold, and 97% within 0.5–2‐fold. There was minimal difference for most drugs in performance between the mixed US and North European pediatric populations. This was partly due to reported studies having low numbers of subjects and under‐representation of some ethnicities. Power calculations showed that to detect a pharmacokinetic difference for the CYP3A4/5 substrates midazolam, sirolimus and tacrolimus between African American and White American children with a power of 80%, 25, 18 and 12 subjects respectively, in each group would be needed. Developing adult and pediatric PBPK models to closely match study populations is important due to their increased regulatory use and with the move to their application in personalized medicine. Such models may also help to bridge some of the ethnic differences not captured in pediatric clinical studies due to the low numbers of subjects.
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BibTeX
@article{johnson2026development,
title = {{Development, Early Verification and Application of a North American Pediatric PBPK Model, Comparison With the North European Pediatric Population}},
author = {Trevor N. Johnson and Fiskani Kondowe and Joyce van der Heijden and Saskia N. de Wildt and Iain Gardner and Karen Rowland Yeo},
journal = {CPT: Pharmacometrics \& Systems Pharmacology},
year = {2026},
month = sep,
doi = {10.1002/psp4.70344},
url = {https://doi.org/10.1002/psp4.70344},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Development, Early Verification and Application of a North American Pediatric PBPK Model, Comparison With the North European Pediatric Population
AU - Trevor N. Johnson
AU - Fiskani Kondowe
AU - Joyce van der Heijden
AU - Saskia N. de Wildt
AU - Iain Gardner
AU - Karen Rowland Yeo
PY - 2026
DA - 2026/09/23
JO - CPT: Pharmacometrics & Systems Pharmacology
DO - 10.1002/psp4.70344
UR - https://doi.org/10.1002/psp4.70344
AB - Physiologically based pharmacokinetic (PBPK) models are increasingly used in pediatric drug development and matching such models to the target population is an important consideration. A US pediatric PBPK model was developed incorporating four sub‐groups describing physiology and enzymatic/transporter levels for White, African American, Hispanic/Latino and Asian subjects. Virtual populations could then be created reflecting the demographics of the clinical study design. Ten different drugs (14 studies) were used to verify the pediatric PBPK model performance. Predicted PK parameters showed reasonable agreement with observed data, 50% of the predicted: observed values were within 0.8–1.25‐fold, 74% within 0.67–1.5‐fold, and 97% within 0.5–2‐fold. There was minimal difference for most drugs in performance between the mixed US and North European pediatric populations. This was partly due to reported studies having low numbers of subjects and under‐representation of some ethnicities. Power calculations showed that to detect a pharmacokinetic difference for the CYP3A4/5 substrates midazolam, sirolimus and tacrolimus between African American and White American children with a power of 80%, 25, 18 and 12 subjects respectively, in each group would be needed. Developing adult and pediatric PBPK models to closely match study populations is important due to their increased regulatory use and with the move to their application in personalized medicine. Such models may also help to bridge some of the ethnic differences not captured in pediatric clinical studies due to the low numbers of subjects.
SN - 2163-8306
ER -