Physiologically Based Pharmacokinetic Modeling of Antibiotics in Children: Perspectives on Model-Informed Precision Dosing

The appropriate use of antibiotics is crucial and involves selecting an optimal dosing regimen based on pharmacokinetic (PK) and pharmacodynamic (PD) indicators. Physiologically based pharmacokinetic (PBPK) modeling is a powerful tool that integrates drugs' physicochemical properties with anatomical and physiological data to predict PK behavior. In pediatric populations, PBPK modeling accounts for developmental changes in organ function, making it particularly useful for optimizing antibiotic dosing across different age groups, from neonates to adolescents. In recent decades, PBPK modeling has been widely applied to predict antibiotic disposition in pediatric patients for various clinical and research purposes. Model-informed precision dosing (MIPD) is an evolving approach that enhances traditional therapeutic drug monitoring by integrating multiple information sources into a mathematical framework. By incorporating PBPK modeling, MIPD could offer a more optimized antibiotic dosing that accounts for PK/PD parameters at the site of infection, improving therapeutic outcomes while minimizing toxicity. This review summarizes currently published pediatric PBPK modeling studies on antibiotics, covering various objectives such as evaluating drug-drug interactions, PK/PD analyses in targeted tissues, predicting PK in specific populations (e.g., maternal/fetal, renal impairment, obesity), and PK predictions for preterm neonates. Based on these reports, the review discusses the implications of PBPK modeling for MIPD in pediatric antibiotic therapy.