Application of Pharmacometric Modelling Towards Precise Dosing in Neonates, Infants and Toddlers: A Scoping Review

BACKGROUND: One of the biggest challenges in the youngest paediatric population (≤ 2 years) is defining a safe and effective dose. Thus, growth and maturation are crucial aspects to consider when pharmacometric (PMX) approaches are applied to estimate key pharmacokinetic parameters that guide dose selection. Derived from this, diverse methodologies and mathematical functions have been proposed. However, there is currently no clear consensus on the use of pharmacometric approaches to guide model-based precision dosing in newborns, infants and toddlers. AIM: This scoping review aimed to provide a comprehensive overview of the current research status on the use of pharmacometric models for precise dosing in neonates, infants and toddlers. METHODS: This scoping review was conducted in accordance with the Joanna Briggs Institute guidelines. MEDLINE and Embase were systematically searched from 1 January 2014 to 14 May 2025. Eligible were studies that applied PMX approaches in the youngest population. Data were extracted to identify scaling and maturation functions applied to guide paediatric dosing. Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review checklist. RESULTS: From 57 studies included, the most commonly applied PMX approaches were population pharmacokinetics (75%) followed by physiologically based pharmacokinetic modelling (25%). Main application areas included antimicrobial therapy (30%), antiepileptic therapy (12%) and antineoplastic therapy (10%). The most commonly used allometric approaches were the fixed allometric scaling exponent based on a power function (37%), diverse exponents on body weight (34%), anatomical and physiological scaling (19%), others (8%) and not reported (2%), with normalisation primarily to standard adult body weight (36%) or the median value (27%) and applied to total clearance, intercompartmental clearance and volume of distribution. Maturation functions were typically incorporated using sigmoidal (49%), power (8%), exponential (7%) or linear functions (4%), depending on post-menstrual or post-natal age. CONCLUSION: This review provides an overview of commonly applied PMX approaches in paediatrics, emphasising the importance of including allometry and maturation functions, and shows the variety of methodological strategies used to guide paediatric dose selection in the youngest population.