应用蒙特卡洛模拟评价和优化普外科抗菌药物给药方案

陈欣, 王莉, 李英, 冯婉玉*

中国药学杂志 ›› 2013, Vol. 48 ›› Issue (4) : 309-313.

中国药学杂志 ›› 2013, Vol. 48 ›› Issue (4) : 309-313. DOI: 10.11669/cpj.2013.04.016
药物与临床

应用蒙特卡洛模拟评价和优化普外科抗菌药物给药方案

  • 陈欣1, 王莉2, 李英1, 冯婉玉1*
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Use of Monte Carlo Simulation to Estimate and Optimize Treatment Regimens for Antibiotic Administration in General Surgery

  • CHEN Xin1, WANG Li2, LI Ying1, FENG Wan-yu1
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摘要

目的 根据药动/药效(PK/PD)理论应用蒙特卡洛模拟评价和优化普外科的抗菌药物给药方案。方法 调查普外科临床应用抗菌药物的情况,将静脉滴注亚胺培南、左氧氟沙星和阿米卡星各给药方案对大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌进行蒙特卡洛模拟,并计算各方案平均疗程以评价疗效。结果 亚胺培南5种给药方案500 mg bid、500 mg tid、500 mg qid、1.0 g bid和1.0 g tid对大肠埃希菌、肺炎克雷伯菌的CFR值均大于目标值,其中500 mg bid的CFR较小且平均疗程较长;各方案对铜绿假单胞菌、鲍曼不动杆菌的CFR均未达标。左氧氟沙星2种给药方案200 mg bid、400 mg qd和阿米卡星3种给药方案200 mg qd、200 mg bid、400 mg qd对目标菌群的CFR模拟值均未达目标,但计算结果符合浓度依赖型药物特点。结论 亚胺培南5种给药方案对大肠埃希菌、肺炎克雷伯菌的最优方案为500 mg tid;对铜绿假单胞菌、鲍曼不动杆菌效果不理想应考虑联合用药。左氧氟沙星、阿米卡星各方案对目标菌群效果均不理想,应结合药敏实验结果用药或考虑联合用药,浓度依赖型抗菌药物每日2次的传统给药方案不能使血药浓度达到目标,建议调整为每日1次。

Abstract

1.Department of Pharmacy, Peking University People′s Hospital, Beijing 100044;2.Department of Pharmacy, Peking University International Hospital, Beijing 100000

关键词

药动/药效学 / 蒙特卡洛模拟 / 亚胺培南 / 合理用药 / 时间依赖型 / 浓度依赖型

Key words

To estimate and optimize the dosing regimens of antibiotics in general surgery with the utilization of Monte Carlo simulation(MCS) based on PK/PD. METHODS??The mean treatment duration(MTD)of different dosing regimens were gathered from clinical cases. MCS model was used to simulate the regimens against Escherichia coli, Klebsiella pneumonius, Acinetobacter baumannii and Pseudomonas aeruginosa, respectively. RESULTS??The CFRs of 500 mg TID, 500 mg QID, 1.0 g BID and 1.0 g TID imipenem against Escherichia coli and Klebsiella pneumonius were greater than that of 500 mg BID(100% / 99%). Correspondingly, MTD of those regimens achieved CFR 100% were shorter than that of 500 mg BID. The CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa were all less than 90%, the CFRs of 200 mg BID, 400 mg QD levofloxacin and 200 mg QD, 200 mg BID, 400 mg QD amikacin were all below 90%. CONCLUSION??The 5 dosing regimens of imipenem were all effective against Escherichia coli and Klebsiella pneumonius. In consideration of pharmaceutical economics, 500 mg TID was the most rational choice. It suggested drug resistance and promoted combined medication that the CFRs of imipenem against Acinetobacter baumannii and Pseudomonas aeruginosa failed to achieve 90%. Drug resistance was also demonstrated by low CFR values of levofloxacin and amikacin treatments. Nevertheless, results of MCS showed inversely proportional between MTD and CFRs, and displayed obvious dose-dependent characteristics of levofloxacin and amikacin. On the purpose of achieving effective concentration, sufficient dose once a day of levofloxacin and amikacin medication were recommend.

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陈欣, 王莉, 李英, 冯婉玉*. 应用蒙特卡洛模拟评价和优化普外科抗菌药物给药方案[J]. 中国药学杂志, 2013, 48(4): 309-313 https://doi.org/10.11669/cpj.2013.04.016
CHEN Xin, WANG Li, LI Ying, FENG Wan-yu. Use of Monte Carlo Simulation to Estimate and Optimize Treatment Regimens for Antibiotic Administration in General Surgery[J]. Chinese Pharmaceutical Journal, 2013, 48(4): 309-313 https://doi.org/10.11669/cpj.2013.04.016

参考文献

PK/PD,Monte Carlo simulation| imipenem| rational drug therapy| time-dependent| dose-dependent

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