利用蒙特卡洛模拟对不同体质量患者使用头孢菌素类药物预防外科手术部位感染的给药方案优化  

Application of Monte Carlo simulation to optimize the administration of cephalosporins for prevention of surgical site infection in patients with different body weights

作　　者：梁馨玉 刘一[1] 黄琳[1] 封宇飞 LIANG Xin-yu;LIU Yi;HUANG Lin;FENG Yu-fei(Department of Pharmacy,Peking University People's Hospital,Beijing 100044,China)

机构地区：[1]北京大学人民医院药剂科,北京100044

出　　处：《中国医院药学杂志》2022年第1期54-59,共6页Chinese Journal of Hospital Pharmacy

基　　金：北京大学人民医院研究与发展基金(编号:RDY2019-39)。

摘　　要：目的:应用蒙特卡洛模拟评价和优化不同体质量患者预防外科手术部位感染的头孢菌素类药物给药方案。方法:使用临床常见的给药剂量,以%fT>4MIC为药动学/药效学(PK/PD)目标,选择群体药动学数据为PK参数,通过比较目标菌种的累积反应分数(cumulative fraction of response,CFR),评价疗效和优化出最佳给药方案。结果:正常体质量患者使用头孢唑啉预防金黄色葡萄球菌,在3 h内所有CFR>90%;预防大肠埃希菌,使用2 g在2 h内,或3 g在3 h内有效。超正常体质量患者预防金黄色葡萄球菌,使用2 g在2 h内CFR>90%;预防大肠埃希菌,使用3 g在2 h内CFR>90%。1.5 g头孢呋辛在1 h内CFR>90%。正常体质量患者使用3 g预防金黄色葡萄球菌,大肠埃希菌和凝固酶阴性葡萄球菌时,大部分能在2 h内达到有效预防效果。超正常体质量患者剂量为3 g,预防金黄色葡萄球菌和凝固酶阴性葡萄球菌结果提示2 h内预防有效;预防大肠埃希菌,仅部分结果显示在1 h内CFR>90%。结论:头孢唑啉对不同体质量的患者给药方案不同,正常体质量患者选择"2 g,q2 h"或"2 g,q3 h"的给药方案,超正常体质量患者选择"3 g,q2 h"的给药方案。头孢呋辛对正常和超正常体质量患者均选择"3 g,q2 h"的方案。OBJECTIVE To evaluate and optimize cephalosporins administration regimen for prevention of surgical site infection in patients with different body weights by using Monte Carlo simulation.METHODS Taking the common clinical dosage as the administration scheme and % fT>4 MIC as the pharmacokinetic/pharmacodynamic(PK/PD)target,and selecting the population pharmacokinetic data as the PK parameter,the curative effect was evaluated and the dosing regimen was optimized by comparing the cumulative fraction of response(CFR)of the target bacteria.RESULTS Cefazolin was used to prevent Staphylococcus aureus in normal weight patients,and the CFR was above 90% within 3 h;for Escherichia coli,the same effect could be achieved by using 2 g cefazolin with interval of 2 h or 3 g with interval of 3 h.Staphylococcus aureus was prevented by using 2 g cefazolin in patients with abnormal weight,and the CFR was higher than 90% within 2 h;3 g cefazolin was used to prevent Escherichia coli with the CFR higher than 90% within 2 h.The CFR of 1.5 g cefuroxime was above 90% within 1 h.When using 3 g cefuroxime to prevent Staphylococcus aureus,Escherichia coli and coagulase negative Staphylococcus in normal weight patients,most of the results showed effective prevention within 2 h.Cefuroxime at the dose of 3 g for preventing Staphylococcus aureus and coagulase negative Staphylococcus in patients with abnormal weight was effective within 2 h,while for preventing Escherichia coli,only some results showed the CFR>90% within 1 h.CONCLUSION Cefazolin should be dosed differently for patients with different body weights,2 g,q2 h or 3 g,q3 h for normal weight patients,and 3 g,q2 h for abnormal weight patients.Cefuroxime is less affected by weight,and 3 g,q2 h can be chosen for both normal and abnormal weight patients.

关 键 词：蒙特卡洛模拟 头孢唑啉 头孢呋辛 群体药动学 

分 类 号：R969.1[医药卫生—药理学]