Physiologically-Based Pharmacokinetic Modeling to Support Pediatric Clinical Development: An IQ Working Group...

Area of Science:

• Pharmacokinetics
• Pediatric Drug Development
• Computational Modeling

Background:

• Health authority strategies simplify pediatric drug development.
• Physiologically based pharmacokinetic (PBPK) models are crucial for pediatric dosing and dose validation.

Purpose of the Study:

• Summarize the current status and challenges of PBPK modeling in pediatric drug development.
• Propose an optimized workflow and recommendations for best practices.
• Identify knowledge gaps and challenges in pediatric PBPK model development, especially for neonates.

Main Methods:

• Review of current practices in pediatric PBPK modeling across therapeutic areas.
• Analysis of case examples where PBPK modeling influenced pediatric label extensions.
• Identification of challenges in understanding pediatric drug absorption, distribution, metabolism, and elimination (ADME).

Main Results:

• PBPK modeling is extensively used in pediatric drug development.
• Key challenges exist in understanding pediatric ADME and modeling neonates.
• Case examples demonstrate PBPK's impact on extending drug labels to pediatric populations.

Conclusions:

• An optimized workflow and best practices are proposed for pediatric PBPK modeling.
• Addressing challenges requires a public data repository, real-world data, and microdose studies.
• Further research is needed to improve PBPK models for pediatric populations, particularly neonates.