Department of Pharmacy, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China.
J Antimicrob Chemother. 2022 Oct 28;77(11):3000-3008. doi: 10.1093/jac/dkac265.
Current polymyxin B dosing in children relies on scant data.
To build a population pharmacokinetic (PK) model for polymyxin B in paediatric patients and assess the likely appropriateness of different dosages.
A total of 19 paediatric patients were enrolled to receive intravenous polymyxin B (1.33-2.53 mg/kg/day), and the median age was 12.5 (range 3.2-17.8) years. Serial plasma samples were collected at steady-state and modelled by population PK analysis. Clinical efficacy and nephrotoxicity of polymyxin B treatment were also assessed.
PK data were adequately described by a two-compartment model with first-order elimination, and weight was a significant covariate of polymyxin B clearance. Clinical success occurred in 14 of 19 patients (73.7%) and only one patient developed acute kidney injury. The 28 day mortality was 10.5% (2/19). The steady-state polymyxin B exposure was 36.97 ± 9.84 mg·h/L, lower than the therapeutic exposure of 50-100 mg·h/L. With the AUC24h/MIC target of 50, the dosage of 1.5-3.0 mg/kg/day had a probability of target attainments over 90% when MICs were <0.5 mg/L.
Dose adjustment of polymyxin B needs to consider the MIC of infecting pathogens. Current polymyxin B dosing for paediatric patients may be acceptable when MICs are <0.5 mg/L.
目前儿童多粘菌素 B 的剂量依据的是有限的数据。
建立儿童多粘菌素 B 的群体药代动力学（PK）模型，并评估不同剂量的合理性。
共纳入 19 例接受静脉注射多粘菌素 B（1.33-2.53mg/kg/天）的儿科患者，中位年龄为 12.5 岁（范围 3.2-17.8 岁）。在稳态时采集系列血浆样本，并通过群体 PK 分析进行建模。还评估了多粘菌素 B 治疗的临床疗效和肾毒性。
PK 数据通过具有一级消除的两室模型得到了很好的描述，体重是多粘菌素 B 清除率的显著协变量。19 例患者中有 14 例（73.7%）临床治疗成功，仅 1 例发生急性肾损伤。28 天死亡率为 10.5%（2/19）。稳态多粘菌素 B 暴露量为 36.97±9.84mg·h/L，低于 50-100mg·h/L 的治疗暴露量。当 AUC24h/MIC 目标为 50 时，当 MIC 值<0.5mg/L 时，1.5-3.0mg/kg/天的剂量方案达到目标的概率超过 90%。
多粘菌素 B 的剂量调整需要考虑感染病原体的 MIC 值。当 MIC 值<0.5mg/L 时，目前儿科患者使用的多粘菌素 B 剂量可能是可以接受的。
