Advancing Pediatric Dose Scaling: Strategies, Modeling Approaches, and Clinical Applications
Rachel A Kudgus Lokken1, Sílvia M Illamola2, Kathleen M Job3
1Allucent, Cary, NC 27513, USA.
Pharmaceuticals (Basel, Switzerland)
|July 28, 2026
Summary
Pediatric drug dosing is complex due to developmental changes. Model-informed strategies, including allometry and physiologically based pharmacokinetic (PBPK) modeling, offer improved precision over simple weight-based methods for children.
Area of Science:
- Pharmacology
- Pediatric Drug Development
- Pharmacometrics
Background:
- Pediatric drug dosing presents significant challenges due to developmental variations in physiology and metabolism.
- Accurate dosing is crucial for optimizing drug exposure and response in children.
Purpose of the Study:
- To review evidence-based approaches for pediatric dose selection across developmental stages.
- To evaluate model-informed strategies for individualized pediatric dosing.
Main Methods:
- Conducted a narrative literature review on pediatric dose-scaling, developmental pharmacology, and modeling techniques.
- Included physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) modeling, exposure-response analysis, and regulatory frameworks.
Main Results:
- Simple weight-based scaling is insufficient; allometric scaling with maturation functions improves predictions in infants.
- PBPK and PopPK modeling enable data-driven dose optimization; fat-free-mass (FFM)-based scaling is preferred for children with obesity.
- Obesity, biologics, pharmacogenomics, and critical illness impact pediatric dosing.
Conclusions:
- Pediatric dosing has shifted to integrated model-informed strategies combining physiology, pharmacometrics, and regulatory science.
- Tools like allometry, PBPK, PopPK, and therapeutic drug monitoring aid rational dosing, requiring drug-specific validation, especially for neonates and critically ill children.
Keywords:
PBPK modelingallometric scalingdose scalingmodel-informed drug development (MIDD)neonatalontogenypediatric pharmacokineticspharmacometricspopulation pharmacokineticsMore Related Videos
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