Physiologically-based pharmacokinetic models for children: Starting to reach maturation?

Area of Science:

• Pharmacology
• Pediatric Drug Development
• Mathematical Modeling

Background:

• Pediatric drug dosing requires careful consideration due to developmental changes affecting drug disposition.
• Linear scaling of adult doses can lead to overdosing in children, particularly neonates.
• Physiologically-based pharmacokinetic (PBPK) models offer a solution for predicting drug concentrations in pediatric populations.

Purpose of the Study:

• To review the principles, challenges, and applications of pediatric PBPK models.
• To provide an overview of the current status and future directions in pediatric PBPK modeling.
• To highlight the growing importance of PBPK models in pediatric drug development.

Main Methods:

• Discussion of general pediatric PBPK model principles.
• Identification of challenges encountered during pediatric PBPK model development.
• Highlighting novel applications of pediatric PBPK models.

Main Results:

• Pediatric PBPK models are increasingly utilized, with available physiological parameters and regulatory support.
• Examples exist where PBPK models have replaced or informed pediatric clinical studies.
• The number and predictive performance of pediatric PBPK models still trail behind adult models.

Conclusions:

• Pediatric PBPK modeling is a valuable tool for optimizing drug dosing in children.
• Continued research and development are needed to enhance the predictive accuracy of pediatric PBPK models.
• These models are crucial for informed pediatric drug development and regulatory decision-making.