Prediction of Monoclonal Antibody Pharmacokinetics in Pediatric Populations Using PBPK Modeling and Simulation

作者：Chiara Zunino, Virginie Gualano, Haiying Zhou, Viera Lukáčová, Maxime Le Merdy · 发表于：Pharmaceutics · 年份：2025 · DOI：10.3390/pharmaceutics17070884 · 被引用次数：3 · 研究领域：Biosimilars and Bioanalytical Methods、Monoclonal and Polyclonal Antibodies Research、Pharmaceutical studies and practices

Background: Accurately determining pediatric dosing is essential prior to initiating clinical trials or administering medications in routine clinical settings. In children, ethical considerations demand careful evaluation of both safety and effectiveness. Typically, dosing recommendations for therapeutic proteins, such as monoclonal antibodies (mAbs), are derived from adult dosages using body weight as a scaling factor. However, this method overlooks key physiological and biochemical distinctions between pediatric and adult patients. Therefore, this could lead to the underexposure of mAbs, limiting their efficacy in this population. Additional methods are necessary to predict pediatric doses mechanistically. For small molecules, physiologically based pharmacokinetic (PBPK) models have been extensively used to predict pediatric doses based on physiological age-related changes and enzymes/transporters ontogeny. This study aims to evaluate the ability of PBPK models to predict mAbs’ pediatric exposure. Methods: Three mAbs were used for model development and validation: bevacizumab, infliximab, and atezolizumab. The PBPK models were built using GastroPlus© Biologics module. For each mAb, the PBPK model was developed based on observed data in healthy and/or patient adults. Then, the physiological parameters were scaled to describe the pediatric physiology to predict exposure to the pediatric populations. Predicted plasma concentration–time courses were overlaid with reported obser...