Abstract
The comparative performances of physiologically-based pharmacokinetic (PBPK) modeling and allometric scaling for predicting the pharmacokinetics (PKs) of large molecules in pediatrics are unknown. Therefore, both methods were evaluated for accuracy in translating knowledge of infliximab PKs from adults to children. PBPK modeling was performed using the base model for large molecules in PK-Sim version 7.4 with modifications in Mobi. Eight population PK models from literature were reconstructed and scaled by allometry to pediatrics. Evaluation data included seven pediatric studies (~4-18 years). Both methods performed comparably with 66.7% and 68.6% of model-predicted concentrations falling within twofold of the observed concentrations for PBPK modeling and allometry, respectively. Considerable variability was noted among the allometric models. Therefore, pediatric clinical trial planning would benefit from using approaches that require predictions depending on the specific question i.e., PBPK modeling and allometry.