Datasheet1_Pragmatic physiologically-based pharmacokinetic modeling to support clinical implementation of optimized gentamicin dosing in term neonates and infants: proof-of-concept.docx

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.,

本研究旨在通过结合基于生理药代动力学（PBPK）的实用建模方法与实施决策框架，开发新生儿及婴儿使用庆大霉素的剂量指导原则。研究方法包括：验证一个现有的PBPK模型，该模型使用87名成人、485名儿童和912名新生儿的药代动力学数据，通过视觉预测检查和预测与观察到的药代动力学（PK）参数比进行验证。模型验证通过后，模拟了荷兰儿科药典（DPF）目前推荐的剂量，以及几种替代剂量方案，旨在实现推荐的峰浓度（即新生儿8-12 mg/L，婴儿15-20 mg/L）和谷浓度（即...）。