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Published on: December 3, 2020
Predicting pharmacokinetic food effects using biorelevant solubility media and physiologically based modelling
Hannah M Jones1, Neil Parrott, Gerd Ohlenbusch
1Drug Metabolism and Pharmacokinetics, F Hoffmann-La Roche Ltd, Basel, Switzerland.
Clinical Pharmacokinetics
|November 23, 2006
Summary
Mathematical models accurately predict drug pharmacokinetics, simulating how food intake impacts drug absorption. This research uses biorelevant solubility data to forecast drug exposure under various meal conditions, improving drug development.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Computational Biology and Modeling
Background:
- Food intake significantly alters gastrointestinal physiology, affecting drug absorption.
- Understanding these food effects is crucial for accurate drug pharmacokinetic predictions.
Purpose of the Study:
- To simulate food effects on drug pharmacokinetics using mathematical models.
- To evaluate the predictive accuracy of these models for six drug compounds.
Main Methods:
- Biorelevant solubility testing in simulated gastrointestinal fluids (fasted/fed states).
- Development of physiologically based absorption models (GastroPlus™).
- Simulation of oral drug pharmacokinetics under various feeding conditions.
Main Results:
- Models successfully differentiated minor and significant food effects.
- Simulations accurately predicted observed plasma concentrations and food effects.
- Predicted drug exposure matched experimental data for fasted, fed, and high-fat conditions.
Conclusions:
- Physiologically based absorption models combined with biorelevant solubility data can predict clinical food effects.
- This approach is effective for drugs limited by solubility or dissolution rate.
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