Pragmatic physiologically-based pharmacokinetic modeling to support clinical implementation of optimized gentamicin dosing in term neonates and infants: proof-of-concept

IntroductionModeling and simulation can support dosing recommendations for clinical practice, but a simple framework is missing. In this proof-of-concept study, we aimed to develop neonatal and infant gentamicin dosing guidelines, supported by a pragmatic physiologically-based pharmacokinetic (PBPK) modeling approach and a decision framework for implementation.MethodsAn already existing PBPK model was verified with data of 87 adults, 485 children and 912 neonates, based on visual predictive checks and predicted-to-observed pharmacokinetic (PK) parameter ratios. After acceptance of the model, dosages now recommended by the Dutch Pediatric Formulary (DPF) were simulated, along with several alternative dosing scenarios, aiming for recommended peak (i.e., 8–12 mg/L for neonates and 15–20 mg/L for infants) and trough (i.e.,