Incorporating Ontogeny in Physiologically Based Pharmacokinetic Modeling to Improve Pediatric Drug Development: What...

Area of Science:

• Pharmacology
• Developmental Biology
• Drug Metabolism

Background:

• Pediatric drug disposition is influenced by developmental changes in drug transporters.
• Physiologically based pharmacokinetic (PBPK) models are crucial for predicting pediatric drug exposure.
• Advancements in PBPK modeling are supported by regulatory bodies like the US Food and Drug Administration.

Purpose of the Study:

• To highlight recent findings on the ontogeny of drug transporters in the intestine, liver, and kidney.
• To demonstrate the utility of incorporating transporter ontogeny data into PBPK models for pediatric drug development.
• To address knowledge gaps in developmental biology for improved PBPK prediction confidence.

Main Methods:

• Review of recent data on the ontogeny of drug transporters in key organs (intestine, liver, kidney).
• Application of PBPK modeling incorporating developmental transporter information.
• Case study illustrating the predictive power of PBPK models with new ontogeny data.

Main Results:

• Emerging data on transporter ontogeny provide critical information for PBPK models.
• Incorporating transporter ontogeny data enhances the accuracy of predicting pediatric drug exposure.
• PBPK models utilizing developmental transporter data show significant utility in pediatric drug development.

Conclusions:

• Collaborative efforts have improved understanding of developmental physiology and drug disposition.
• Addressing remaining knowledge gaps is essential for advancing PBPK modeling in pediatric drug development.
• Continued research on transporter ontogeny will enhance the application of PBPK models for children.