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Age-dependent oral drug absorption in children: Assessment of a bottom-up modelling approach

Fabian Winter1, Jonas Lange1, Sandra Klein1

  • 1Department of Pharmacy, University of Greifswald, Greifswald 17489, Germany.

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V
|July 24, 2025
PubMed

Insights

This study developed a paediatric PBPK model for essential medicines, improving drug dosing predictions in children. The model enhances accuracy by using age-specific parameters and in vitro data, addressing key challenges in paediatric pharmacokinetics.

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Paediatric Pharmacology
  • Computational Modelling

Background:

  • Paediatric drug development faces unique physiological and ethical hurdles.
  • Physiologically Based Pharmacokinetic (PBPK) modelling aids in predicting drug absorption and optimizing paediatric dosing.
  • Existing models often require interpolation or scaling due to limited paediatric-specific data.

Purpose of the Study:

  • To refine PBPK modelling for paediatric applications by developing a customized paediatric PBPK (pPBPK) model.
  • To incorporate age-specific gastrointestinal parameters for four distinct paediatric age groups.
  • To investigate the effect of food on drug absorption, considering bile and excipient solubilisation.

Main Methods:

  • Developed a PK-Sim-based pPBPK model for four WHO Essential Medicines for Children: paracetamol, ibuprofen, darunavir, and itraconazole.
  • Integrated age-specific gastrointestinal parameters, minimizing interpolation needs.
  • Incorporated biorelevant in vitro dissolution and solubility data, and extended absorption models for food effects.

Main Results:

  • The pPBPK model demonstrated reliability across various paediatric age groups when validated with clinical pharmacokinetic data.
  • Sensitivity analyses identified key parameters influencing paediatric drug pharmacokinetics, including gastric emptying time and bile salt concentration.
  • The study successfully addressed gaps in understanding paediatric intestinal parameters for pPBPK modelling.

Conclusions:

  • The developed pPBPK model shows significant potential for informing paediatric dosing strategies.
  • This approach enhances prediction accuracy by utilizing specific paediatric parameters and in vitro data.
  • The research contributes to overcoming challenges in paediatric drug development and optimizing medication for children.

Keywords:
Absorption modellingFood effect modellingGastrointestinal physiologyPBPKPK-SimPaediatric formulationsScalingSimulated paediatric breakfast mealspPBPK

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