PII-119 - EVALUATING AND OPTIMIZING ALLOMETRIC SCALING APPROACHES FOR PREDICTING PEDIATRIC EXPOSURES OF INTRAVENOUSLY ADMINISTERED SMALL MOLECULES AND BIOLOGICS FROM ADULT DATA

J. Chen Gan¹, S. Drescher²; ¹UCSD, California, USA, ²Pfizer, Inc., La Jolla, CA, USA.

Background: Conducting pediatric clinical trials to understand drug disposition in children presents significant challenges, including difficulties in patient recruitment and limitations on blood sampling. Previous attempts have used allometric scaling as a method to predict pediatric clearances based on adult data, but this approach has not been extended to biologics or children < 2 years old (Momper et al, 2013; Liu et al, 2016). The aim of this analysis was to evaluate the performance of allometric scaling approaches across drug modalities and pediatric ages.

Methods: FDA labels of 48 intravenous drugs approved from 2002 to 2024 were reviewed to extract adult/pediatric indications, dosing information, elimination routes, observed adult/pediatric clearances, and pediatric age/body weights. Multiple clearance values were extracted for drugs where pediatric data was divided into age/weight groups. When not reported, clearances were derived from dose-normalized AUC. Pediatric clearances were predicted with an allometric equation standardized to a 70 kg adult and tested across a range of scaling exponents (0.1 to 1). The proximity of observed pediatric clearances to predicted values was assessed via linear regression.

Results: We extracted 116 clearance values (69 small molecules, 47 biologics) from pediatric patients aged 18 days to 16.6 years (body weights: 2.8-84 kg). Ages were grouped as: < 2, 2-5, 6-11, and 12-17 years. In all age groups and drug modalities, the predicted clearances were most sensitive to changes in the allometric scaling exponent in patients < 2 years. An exponent of 0.63 to 0.64 yielded the most predicted values within two-fold of observed clearances in all age groups. The performance of allometric scaling approaches was similar for renally- and hepatically-cleared small molecule clearances, suggesting allometry effectively captures the ontogenesis of relevant organ systems. Biologic products had a higher coefficient of determination (R2=0.9891) between observed and predicted pediatric clearances compared to small molecule drugs (R2=0.8668).

Conclusion: Allometric scaling is an appropriate method to predict pediatric exposures across all age groups and drug modalities. For this data, optimized performance for predicting clearance is achieved with an allometric exponent between 0.63 and 0.64.