Jirasomprasert Totsapol, Tian Li-Yuan, You Dian-Ping, Wang Ya-Kun, Dong Lei, Zhang Ya-Hui, Hao Guo-Xiang, van den Anker John, Wu Yue-E, Tang Bo-Hao, Zhao Wei, Zheng Yi
Department of Clinical Pharmacy, Institute of Clinical Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Respiratory Care, Children's Hospital of Hebei Province affiliated to Hebei Medical University, Shijiazhuang, China.
Paediatr Drugs. 2025 Jan;27(1):91-102. doi: 10.1007/s40272-024-00664-4. Epub 2024 Nov 27.
We aimed to determine the piperacillin disposition and optimize the dosing regimens for infants and children with pneumonia.
An opportunistic sampling strategy was used in this pharmacokinetic study. High-performance liquid chromatography was used to measure the concentrations of piperacillin in plasma samples. A population pharmacokinetic model was conducted using NONMEM.
The pharmacokinetic data of 90 samples from 64 infants and children with pneumonia (age range: 0.09-1.72 years for infants and 2.12-11.10 years for children) were available. A two-compartment model with first-order elimination was the most suitable model to describe the population pharmacokinetics of piperacillin. A covariate analysis indicated that body weight and age were significant factors affecting clearance. Monte Carlo simulations showed that a 50-mg/kg every 8 h or every 12 h dosing regimen results in underdosing. Results both in infants and children showed that an extended infusion (3 h) of various dosing regimens (80, 100, or 130 mg/kg) three times daily or a 300-mg/kg continuous infusion can reach a therapeutic level based on the chosen target for the probability of target attainment threshold of 70%, 80%, and 90% at minimum inhibitory concentration breakpoints of 8 mg/L and 16 mg/L.
A population pharmacokinetic model was obtained to evaluate the disposition of piperacillin, and the optimal dosing regimens were provided for use in infants and children with pneumonia.
我们旨在确定哌拉西林的处置情况，并优化肺炎婴幼儿和儿童的给药方案。
本药代动力学研究采用了机会抽样策略。使用高效液相色谱法测量血浆样本中哌拉西林的浓度。使用NONMEM进行群体药代动力学模型分析。
获得了64例肺炎婴幼儿和儿童（婴儿年龄范围：0.09 - 1.72岁，儿童年龄范围：2.12 - 11.10岁）的90份样本的药代动力学数据。具有一级消除的二室模型是描述哌拉西林群体药代动力学的最合适模型。协变量分析表明体重和年龄是影响清除率的重要因素。蒙特卡洛模拟显示，每8小时或每12小时50mg/kg的给药方案会导致剂量不足。婴幼儿和儿童的结果均表明，基于选定的目标，在最低抑菌浓度断点为8mg/L和16mg/L时，每日三次延长输注（3小时）不同给药方案（80、100或130mg/kg）或300mg/kg持续输注，在达到目标概率阈值70%、80%和90%时可达到治疗水平。
获得了一个群体药代动力学模型以评估哌拉西林的处置情况，并为肺炎婴幼儿和儿童提供了最佳给药方案。
