Can PBPK Modeling Streamline Food Effect Assessments?

Area of Science:

• Pharmacokinetics
• Drug Development
• Computational Modeling

Background:

• Physiologically based pharmacokinetic (PBPK) modeling is established for drug-drug interactions and product labeling.
• PBPK models are increasingly used for oral drug absorption and product quality assessments.
• Existing PBPK applications show success in characterizing oral drug product absorption.

Purpose of the Study:

• To explore the utility of PBPK modeling in predicting food-drug interactions.
• To assess the potential of PBPK models for streamlining food effect evaluations in clinical settings.
• To propose a workflow for integrating PBPK into food effect assessments during drug development.

Main Methods:

• Reviewing existing literature on PBPK model applications in oral absorption.
• Analyzing studies that compare PBPK food effect predictions with clinical data.
• Identifying key food effect mechanisms (gastric emptying, luminal solubilization) modeled by PBPK.
• Synthesizing findings to propose a PBPK-driven workflow for food effect assessment.

Main Results:

• PBPK models have successfully characterized oral drug absorption.
• Multiple publications demonstrate PBPK's ability to predict food effects.
• Commonly modeled food effect mechanisms include delayed gastric emptying and altered luminal solubilization.
• PBPK predictions show good agreement with clinical food effect data.

Conclusions:

• PBPK modeling offers a viable approach to streamline food effect assessments.
• The proposed workflow can aid in optimizing clinical development strategies.
• PBPK can reduce the need for certain clinical studies related to food effects.
• This approach is applicable across different Biopharmaceutics Classification System classes.