Investigation of Monoclonal Antibody Pharmacokinetics in Pediatric Population and Characterization Using a Platform...

This study aimed to investigate the impact of age on pediatric PK of mAbs and develop a platform PBPK model to support optimal dosing of mAbs in pediatric patients. After extensive literature review 49 mAbs were identified as approved for pediatric use, but only 17 had adequate PK data to support the investigation. It was found that pediatric patients exhibit 20-40% lower initial concentration (i.e. C₀) compared to adults following the same body weight normalized dose. For mAbs demonstrating linear PK, a similar rate of bodyweight normalized clearance was observed between adult and pediatric patients aged 2 years and above, while a faster clearance per kg bodyweight (up to 45% higher) was seen for infants and neonates. The majority of mAbs that demonstrate nonlinear PK were found to have faster bodyweight normalized clearance (up to 350% higher) in pediatric patients. A platform PBPK model was developed to characterize the PK of mAbs in pediatric patients across all age groups. The model was able to adequately (%PE < 35) characterize plasma PK of 11 mAbs with linear PK in pediatric patients aged 0.13 to 17 years following intravenous or subcutaneous administration. The developed model was able to apriori predict antibody PK reasonably well (%PE < 35). The PBPK model was integrated into an interactive web-based R Shiny application ( http://40.67.147.7/ ). The app allows individuals with minimal pharmacometrics expertise to simulate the PK of mAbs in pediatric patients and personalize the dosing of mAbs in patients with sparse PK data from therapeutic drug monitoring.