A physiologically based pharmacokinetic model of the minipig: data compilation and model implementation

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Preclinical Pharmaceutical Research
• Computational Biology

Background:

• Physiologically-based pharmacokinetic (PBPK) modeling is crucial for drug development, integrating in vitro data to predict in vivo exposure.
• The Göttingen minipig is an emerging large animal model in preclinical studies due to its human-like physiology, replacing traditional models.
• A significant knowledge gap exists regarding PBPK models for the Göttingen minipig.

Purpose of the Study:

• To review available physiological data for establishing a Göttingen minipig PBPK model.
• To identify knowledge gaps in physiological parameters for minipig PBPK modeling.
• To develop and validate a preliminary PBPK model for the Göttingen minipig.

Main Methods:

• Compilation and assessment of existing physiological and anatomical data for Göttingen minipigs.
• Development of a preliminary PBPK model incorporating the gathered physiological database.
• Simulation of plasma concentrations for two model drugs administered via intravenous and oral routes.

Main Results:

• The developed PBPK model demonstrated validity, with simulated drug concentrations aligning with observed plasma levels.
• The model provides a foundational framework for simulating drug behavior in Göttingen minipigs.
• Identified gaps in physiological data necessitate future model refinement.

Conclusions:

• The preliminary PBPK model for Göttingen minipigs is a valuable tool for pharmaceutical research and development.
• The model's accuracy is expected to improve with the incorporation of additional physiological data.
• This PBPK model supports informed decision-making in preclinical drug development using minipigs.