Predicting the pharmacokinetics and food effect of oral drug products using the dynamic gastrointestinal model (DGM)

Matthias Manne Knopp, Jacob Rune Jørgensen, Laila Tognarelli Hansen, Anette Müllertz*

*Corresponding author for this work

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Abstract

The pharmacokinetics (PK) of oral drug compounds are often significantly altered by food intake and evaluating this effect, as required by regulatory agencies, typically involves costly and time-consuming clinical trials. This study used the Dynamic Gastrointestinal Model (DGM), an advanced in vitro system simulating both biochemical and mechanical aspects of the human upper gastrointestinal tract, to predict plasma concentration–time profiles (PK profiles) and food effect of three immediate release oral drug products. The drug products, containing cinnarizine (CIN), diclofenac potassium (DIC) or paracetamol (PAR), were processed in the DGM mimicking the fasted and fed state clinical protocols and the resulting intestinal drug dissolution profiles were modelled (by convolution) to achieve the predicted PK profiles. The predicted PK profiles in both the fasted and fed state were in accordance with the observations in clinical trials, capturing both the positive food effect for CIN and the negative food effects for DIC and PAR. These findings demonstrate the ability of the DGM to provide insights into the PK performance and food effect of oral drug products.

Original languageEnglish
Article number114723
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume212
ISSN0939-6411
DOIs
Publication statusPublished - 2025

Bibliographical note

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© 2025

Keywords

  • Bioequivalence
  • Biopharmaceutics
  • Biorelevant
  • Dynamic gastrointestinal model (DGM)
  • Food effect
  • Gastrointestinal model
  • IVIVC
  • PBPK
  • Predicting pharmacokinetics

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