利奈唑胺在败血症新生儿中的群体药动学模型构建  

Establishment of a population pharmacokinetic model for linezolid in neonates with sepsis

作　　者：冯宗太[1] 唐莲[2] 杨祖铭[1] 高楚楚 李家慧 蔡燕[1] 段露芬 FENG Zong-Tai;TANG Lian;YANG Zu-Ming;GAO Chu-Chu;LI Jia-Hui;CAI Yan;DUAN Lu-Fen(Department of Pharmacy,Suzhou Municipal Hospital/Affiliated Suzhou Hospital of Nanjing Medical University/Gusu School of Nanjing Medical University,Suzhou,Jiangsu 215002,China)

机构地区：[1]苏州市立医院/南京医科大学附属苏州医院/南京医科大学姑苏学院新生儿科,江苏苏州215002 [2]苏州市立医院/南京医科大学附属苏州医院/南京医科大学姑苏学院药剂科,江苏苏州215002

出　　处：《中国当代儿科杂志》2024年第11期1162-1168,共7页Chinese Journal of Contemporary Pediatrics

基　　金：江苏省医学会科研专项资金[SYH-32034-0080(20230027)];南京医科大学姑苏学院科研项目(GSKY20230201)。

摘　　要：目的建立利奈唑胺在新生儿中的药动学模型并优化给药方案。方法前瞻性收集64例使用利奈唑胺抗感染治疗的败血症新生儿为研究对象,采用液相色谱串联质谱法检测血药浓度,收集临床资料,采用非线性混合效应建模法建立群体药动学(population pharmacokinetic,PPK)模型,采用蒙特卡洛模拟和评价不同特征患儿的最佳给药方案。结果利奈唑胺在新生儿体内的药动学特性可用一个具有一级消除的单室模型来描述,表观分布容积和清除率的群体典型值分别为0.79 L和0.34 L/h。拟合优度、可视化验证及自举法结果表明,模型稳健,参数估算及预测结果可靠。蒙特卡洛模拟显示新生儿利奈唑胺最佳给药方案,胎龄(gestational age,GA)28周6 mg/kg,q8h;GA 32周8 mg/kg,q8h;GA 34~37周9 mg/kg,q8h;GA 40周11 mg/kg,q8h。结论该研究建立的PPK模型可为新生儿利奈唑胺的个体化给药提供参考,GA和用药时体重是影响新生儿利奈唑胺清除率的显著性因素。Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen.Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug.Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic(PPK)model.Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features.Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively.The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction.Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age(GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA.Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates.GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

关 键 词：败血症 利奈唑胺 群体药动学 治疗药物监测 蒙特卡洛模拟 新生儿 

分 类 号：R722.131[医药卫生—儿科]