摘要
目的:应用蒙特卡洛模拟探讨卡泊芬净在儿童患者中的给药方案,为个体化给药提供参考。方法:根据年龄对儿童患者进行分组,结合卡泊芬净对念珠菌和曲霉菌的最低抑菌浓度(minimum inhibitory concentration,MIC)分布情况,以及卡泊芬净在儿童患者中的群体药动学参数,采用Crystal Ball 11.1.2.2软件对不同年龄组患儿的不同给药方案应用蒙特卡洛模型进行模拟,以达标概率(probability of targe attainment,PTA)和累积反应分数(cumulative fraction of response,CFR)作为评价指标。结果:给予卡泊芬净每日维持剂量50 mg/m2,最大日剂量为70 mg,不同年龄组,对于念珠菌感染,当MIC≤0.06μg/ml时,可满足治疗效果;在上述情况下,治疗白色念珠菌、光滑念珠菌和热带念珠菌可满足CFR> 90%,对克柔念珠菌的CFR为80%~90%,对近平滑念珠菌的CFR <20%;而对于曲霉菌感染,MIC≤0.015μg/ml时,才可满足治疗效果,但CFR均<80%。结论:卡泊芬净对白色念珠菌、光滑念珠菌及热带念珠菌的活性强,CFR与MIC分布有关;结合群体药动学和蒙特卡洛模型,推行个体化给药方案,可最终实现个体患儿的理想治疗效果。
OBJECTIVE: To probe into the administration regimen of caspofungin in children based on Monte Carlo simulation,so as to provide reference for individualized administration. METHODS: Pediatric patients were grouped according to age,combined with the distribution of the minimum inhibitory concentration( MIC) of caspofungin against Candida and Aspergillus and the population pharmacokinetic parameters of caspofungin in pediatric patients,Crystal Ball11. 1. 2. 2 software was used to simulate different administration regimens of children in different age groups based on Monte Carlo model. The probability of targe attainment( PTA) and cumulative fraction of response( CFR) were used as evaluation indicators. RESULTS: The daily maintenance dose of caspofungin was 50 mg/m2,and the maximum daily dose was 70 mg. In different age groups,for Candida infection,when the MIC value was ≤0. 06 μg/ml,the therapeutic effect could be satisfied. In this case,treatment of C. albicans,C. glabrata and C. tropicalis could meet CFR > 90%,while CFR values for C. krusei ranged from 80% to 90% and < 20% for C. glabrata. In contrast,for Aspergillus infection,MIC values ≤ 0. 015 μg/ml were required to meet the therapeutic effect,but none of the CFR values reached80%. CONCLUSIONS: Caspofungin had strong activity against C. albicans,C. glabrata and C. tropicalis,and its CFR value is related to the distribution of MIC. The combination of population pharmacokinetics and Monte Carlo model,and the implementation of individualized dosing regimens can ultimately achieve the desired therapeutic effect in individual children.
作者
刘艳辉
贾丽丽
丁翔宇
张古英
LIU Yanhui;JIA Lili;DING Xiangyu;ZHANG Guying(Dept.of Pharmacy,Children’s Hospital of Hebei Province,Hebei Shijiazhuang 050031,China;Dept.of Basic Medicine,Shijiazhuang Medical College,Hebei Shijiazhuang 050000,China)
出处
《中国医院用药评价与分析》
2021年第6期646-649,共4页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
河北省医学科学研究课题计划(No.20190810)。
关键词
卡泊芬净
蒙特卡洛模型
念珠菌感染
曲霉菌感染
儿童
Caspofungin
Monte Carlo simulation
Candida infection
Aspergillus infection
Children
