Translational PBPK/PD modeling in drug discovery: A CRO perspective

Area of Science:

• Pharmacology and Drug Discovery
• Computational Biology
• Preclinical Research

Background:

• Physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) modeling is integral to modern drug discovery.
• These models facilitate advanced data integration, considering species-specific physiology and target pharmacology.
• The application of PBPK/PD is expanding within integrated drug discovery (IDD) collaborations.

Purpose of the Study:

• To present a preclinical contract research organization (CRO) perspective on translational PBPK/PD modeling.
• To outline the applications, benefits, and challenges of these modeling approaches in IDD.
• To examine the impact of PBPK/PD on the role of the drug metabolism and pharmacokinetics project representative (DPR) within CROs.

Main Methods:

• Review of PBPK/PD applications in preclinical contract research.
• Analysis of PBPK/PD impact on integrated drug discovery workflows.
• Case studies or examples illustrating PBPK/PD implementation within CRO-sponsor partnerships.

Main Results:

• Translational PBPK/PD modeling offers significant benefits in data integration and predictive accuracy.
• Challenges include data availability, model complexity, and regulatory acceptance.
• The role of the DPR has evolved to incorporate advanced modeling and data interpretation skills.

Conclusions:

• Adoption of translational PBPK/PD approaches strengthens sponsor-CRO partnerships.
• These methods foster data-driven decision-making throughout the drug discovery process.
• Optimized resource utilization and improved project outcomes are key advantages.