哌拉西林他唑巴坦在肾内科患者中的群体药动学和蒙特卡罗模拟  

Population pharmacokinetics of piperacillin tazobactam in patients in department of nephrology and Monte Carlo simulation

作　　者：孙梦茹[1,2] 陈荣[1,2] 钱卿[1,2] 王明丽[1,2] 邹素兰[1,2] 

机构地区：[1]常州市第一人民医院 [2]苏州大学附属第三人民医院,江苏常州213003

出　　处：《中国医院药学杂志》2015年第2期136-141,共6页Chinese Journal of Hospital Pharmacy

基　　金：江苏省药学会奥赛康临床药学科研项目(编号:201206)

摘　　要：目的:建立哌拉西林他唑巴坦在肾内科患者中的群体药动学模型,应用蒙特卡罗模拟优化其给药方案,以促进个体化给药。方法:采用高效液相色谱法测定50名肾内科患者静脉滴注哌拉西林-他唑巴坦的血清浓度310例次并收集相关临床指标,运用非线性混合效应模型(NONMEM)程序建立群体药动学模型。采用蒙特卡罗模拟(Monte Carlo simulation,MCS)比较哌拉西林他唑巴坦的不同给药方案对不同MIC群体的药效学目标到达。结果:哌拉西林、他唑巴坦的药动学符合一室模型,群体典型值及个体间差异(Between Subject Variability,BSV)分别为:哌拉西林CL/F=13.74 L·h-1,BSV=11.1%;V/F=21.69 L,BSV=8.0%,他唑巴坦CL/F=9.32 L·h-1,BSV=9.11%;V/F=16.0L,BSV=5.28%;固定效应参数中,肌酐清除率对参数有影响。对于MIC值较大的细菌,延长输注的给药方案获得了更高的目标的累积反应分数(CFR)。结论:群体药动学模型和蒙特卡罗模拟,可为调整哌拉西林他唑巴坦的治疗方案提供有效的分析手段。OBJECTIVE To construct a population pharmacokinetics model of piperacillin tazobactam in patients in department nephrology by applying optimized dosing regimen of piperacillin tazobactam to promote individualized medication.METHODS From50 patients in department of nephrology intravenously dripped piperacillin-tazobactam,a total of 310 blood samples were collected to determine relevant clinical parameters.Nonlinear mixed-effect model（NONMEM）was used to construct a population pharmacokinects model.Monte Carlo simulation（MCS）was performed to evaluate whether pharmacodynamics targets were achieved in different MIC populations in different dosing regimens of piperacillin/tazobactam.RESULTS The pharmacokinetic profile of piperacillin and tazobactam fitted best to one-compartment model.The population typical values and between subject variability were CL/F=13.74 L·h-1,BSV=11.1%;V/F=21.69 L,BSV=8.0%for piperacillin,and CL/F=9.32 L·h-1,BSV=9.11%;V/F=16.0L,BSV=5.28%for tazobactam.In fixed effect variables,creatinine clearance had significant effects on pharmacokinetic parameters.Prolonged infusion of piperacillin-tazobactam yielded greater cumulative fraction of response（CFR）for bacteria with higher MIC values.CONCLUSION The population pharmacokinetics and Monte Carlo simulation can provide useful analytic measures for adjusting therapeutic regimen of piperacillin tazobactam.

关 键 词：哌拉西林 他唑巴坦 群体药动学 蒙特卡罗模拟 

分 类 号：R969[医药卫生—药理学]