应用蒙特卡洛模拟评价和优化普外科抗菌药物给药方案  

Use of Monte Carlo Simulation to Estimate and Optimize Treatment Regimens for Antibiotic Administration in General Surgery

作　　者：陈欣[1] 王莉 李英[1] 冯婉玉[1] 

机构地区：[1]北京大学人民医院药剂科,北京100044 [2]北大国际医院,北京100000

出　　处：《中国药学杂志》2013年第4期309-313,共5页Chinese Pharmaceutical Journal

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 mgtid、500 mg qid、1.0g bid和1.0g 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。OBJECTIVE ： To estimate and optimize the dosing regimens of antibiotics in general surgery with the utilization ot 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 bau- mannii 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 treat- ments. 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 levoflox- acin and amikacin medication were recommend.

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 

分 类 号：R969.3[医药卫生—药理学]