Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Centre of Excellence for Pediatric Infectious Diseases and Vaccines, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Int J Infect Dis. 2021 Aug;109:230-237. doi: 10.1016/j.ijid.2021.06.052. Epub 2021 Jun 27.
The aim of this study was to describe the population pharmacokinetics of intravenous colistin use in children and to propose optimal dosage regimens.
A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Phoenix 64 version 8.3 was used for the PPK analysis. Simulations were performed to estimate the probability of target attainment for patients achieving target plasma colistin average steady-state concentrations (C).
A total of 334 plasma colistin concentrations were obtained from 79 pediatric patients with a median age (interquartile range) of 2.6 years (0.8-6.8 years); 73 (92.4%) were admitted to intensive care units. Colistin pharmacokinetics were adequately described by a one-compartment model with first-order elimination along with serum creatinine (SCr) as a significant covariate in colistin clearance. The simulation demonstrated that the recommended dose of 5 mg of colistin base activity (CBA)/kg/day resulted in 18.2-63.0% probability of achieving a target C of 2 mg/l. With a lower targeted C of 1 mg/l, colistin dosing with 7.5 mg and 5 mg of CBA/kg/day were adequate for children with SCr levels of 0.1-0.3 mg/dl and >0.3 mg/dl, respectively.
SCr is a significant covariate in colistin clearance in children. Colistin dosing should be selected according to the patient's SCr level and the desired target C.
本研究旨在描述儿童静脉注射黏菌素的群体药代动力学特征，并提出最佳剂量方案。
进行了一项前瞻性、多中心的群体药代动力学（PPK）研究。使用 Phoenix 64 版本 8.3 进行 PPK 分析。模拟用于估计达到目标血浆黏菌素平均稳态浓度（C）的患者的达标概率。
从 79 名儿科患者中获得了 334 个血浆黏菌素浓度，中位数（四分位距）年龄为 2.6 岁（0.8-6.8 岁）；73 例（92.4%）入住重症监护病房。黏菌素药代动力学通过一室模型和一级消除来描述，血清肌酐（SCr）是黏菌素清除率的显著协变量。模拟表明，推荐的 5mg 黏菌素碱基活性（CBA）/kg/天剂量可使达到 2mg/l 目标 C 的概率为 18.2-63.0%。如果目标 C 较低（1mg/l），则对于 SCr 水平为 0.1-0.3mg/dl 和>0.3mg/dl 的儿童，分别使用 7.5mg 和 5mg 的 CBA/kg/天剂量可以达到足够的黏菌素浓度。
SCr 是儿童黏菌素清除率的一个重要协变量。黏菌素剂量应根据患者的 SCr 水平和所需的目标 C 进行选择。
