应用蒙特卡罗模拟优化哌拉西林/他唑巴坦的给药方案

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (8): 901-905.

应用蒙特卡罗模拟优化哌拉西林/他唑巴坦的给药方案

叶龙强¹, 蔡挺²

¹宁波市医疗中心李惠利医院ICU,宁波 315040,浙江;
² 宁波市第二医院呼吸内科,宁波 315010,浙江

收稿日期:2010-04-12 修回日期:2010-08-01 出版日期:2010-08-26 发布日期:2020-09-17
通讯作者: 蔡挺,男,主任医师,研究方向:感染与重症监护。E-mail: nbicu@tom.com
作者简介:叶龙强,男,硕士,主治医师,研究方向:重症感染。Tel: 13567480636 E-mail: longqiangy@126.com
基金资助:
浙江省医药卫生科技计划(2006B116);宁波市自然科学基金(2006A610037)

Use of Monte Carlo simulation to optimize dosing regimens for Piperacillin-tazobactam

YE Long-qiang¹, CAI Ting²

¹Department of Intensive Care Unit,Ningbo Medical Center Lihuili Hospital,Ningbo 315040,Zhejiang,China;
²Department of Respiration,Ningbo No.2 Hospital, Ningbo 315010,Zhejiang,China

Received:2010-04-12 Revised:2010-08-01 Online:2010-08-26 Published:2020-09-17

摘要/Abstract

摘要： 目的: 评价哌拉西林/他唑巴坦的延长输注和持续输注给药方案对革兰阴性杆菌的药效学。方法: 测定本院2008年1月至2008年6月4种革兰阴性杆菌(大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌及铜绿假单胞菌)的MIC,应用10000例蒙特卡罗模拟(MCS)分析比较哌拉西林/他唑巴坦的延长输注(PI)、持续输注(CI)与传统给药方案的药效学目标到达。结果: 对于大肠埃希菌和肺炎克雷伯菌,只有 4.5 g q 6 h(PI)的给药方案能达到90%以上的累积反应分数(CFR),分别为 98.4%、91.0%。对于鲍曼不动杆菌和铜绿假单胞菌,没有一种给药方案能达到最佳的CFR。持续输注给药方案 9.0 g CI与传统给药方案 4.5 g q 8 h相比,获得更高的CFR。4.5 g q 8 h(PI)、4.5 g q 6 h(PI)与传统给药方案相比,对4种革兰阴性杆菌获得更高的CFR。结论: 哌拉西林/他唑巴坦延长输注及持续输注方案较常规方案更优,可作为临床的经验给药方案。

关键词: 蒙特卡罗模拟, 哌拉西林/他唑巴坦, 革兰阴性杆菌, 药效学

Abstract: AIM: To evaluate the pharmacodynamic profiling of prolonged and continuous infusion dosing regimens of Piperacillin-tazobactam against gram-negative bacteria.METHODS: Minimum inhibitory concentrations for Escherichia coli,Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa from Jan 2008 to Jun 2008 in hospital were determined. A 10000-subject Monte Carlo simulation was performed to calculate pharmacodynamic target attainment for prolonged, continuous and traditional dosing regimens of Piperacillin-tazobactam.RESULTS: Against Escherichia coli and Klebsiella pneumoniae, only Piperacillin-tazobactam 4.5 g every 6 hours (3-h infusion) achieved cumulative fraction of response (CFR) of greater than 90%, 98.4% and 91.0%,respectively. No regimen achieved optimum CFR against Acinetobacter baumannii and Pseudomonas aeruginosa. Continuous infusion Piperacillin-tazobactam 9.0 g every 24 hours led to higher CFR than 4.5 g every 8 hours (30-min infusion). Compared with traditional regimen (30-min infusion), prolonged infusion Piperacillin-tazobactam 4.5 g every 8 hours and 4.5 g every 6 hours yielded greater CFR. CONCLUSION: Prolonged and continuous infusion Piperacillin-tazobactam is superior to traditional regimens and should be recommended as empirical therapy against common gram-negative bacteria.

Key words: Monte Carlo simulation, Piperacillin-tazobactam, Gram-negative bacteria, Pharmacodynamics

中图分类号:

R911

叶龙强, 蔡挺. 应用蒙特卡罗模拟优化哌拉西林/他唑巴坦的给药方案[J]. 中国临床药理学与治疗学, 2010, 15(8): 901-905.

YE Long-qiang, CAI Ting. Use of Monte Carlo simulation to optimize dosing regimens for Piperacillin-tazobactam[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(8): 901-905.

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