药代动力学/药效动力学模型结合蒙特卡罗模拟优化儿童耐甲氧西林金黄色葡萄球菌感染的万古霉素给药方案

张宏亮, 黄振光, 丘岳, 李萌, 刘滔滔

中国药学杂志 ›› 2017, Vol. 52 ›› Issue (3) : 217-220.

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中国药学杂志 ›› 2017, Vol. 52 ›› Issue (3) : 217-220. DOI: 10.11669/cpj.2017.03.011
论著

药代动力学/药效动力学模型结合蒙特卡罗模拟优化儿童耐甲氧西林金黄色葡萄球菌感染的万古霉素给药方案

  • 张宏亮a, 黄振光a, 丘岳a, 李萌b, 刘滔滔a*
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Optimizing Vancomycin Regimen in Children with MRSA Infections Based on PK/PD Model and Monte Carlo Simulation

  • ZHANG Hong-liang a, HUANG Zhen-guang a, QIU Yuea, LI Mengb, LIU Tao-tao a*
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摘要

目的 优化儿童耐甲氧西林金黄色葡萄球菌(MRSA)感染的万古霉素的经验给药方案。方法 根据万古霉素的药代动力学/药效动力学(PK/PD)模型,对不同剂量的万古霉素的给药方案进行蒙特卡罗模拟模拟,从而得出最佳的给药方案。结果 随着万古霉素的日剂量增加,预期AUC0-24/MIC> 400的百分比亦相应增加。当MIC为0.5 mg·L-1时,万古霉素的剂量为35 mg·kg-1·d-1,AUC0-24/MIC> 400的比例即可达99.41%。当MIC为1 mg·L-1时,剂量增加至65 mg·kg-1·d-1时, AUC0-24/MIC> 400才能达到 97.55%。当MIC为2 mg·L-1及以上时,没有剂量能达到AUC0-24/MIC>400的要求。结论 儿童MRSA感染时,当MIC为0.5 mg·L-1时,万古霉素的经验治疗剂量应大于35 mg·kg-1·d-1;当MIC为1.0 mg·L-1时,推荐剂量应大于65 mg·kg-1·d-1

Abstract

OBJECTIVE To optimize vancomycin regimen in children with MRSA infection. METHODS Vancomycin AUC0-24/MIC predictions were performed across a range of dosages (20-70 mg·kg-1·d-1) using a Monte Carlo simulation (n=10 000). AUC0-24 was calculated as daily dose divided by vancomycin clearance, and daily dose was fixed for a given simulation. The MIC distribution for MRSA was obtained from the RESULTS of clinical laboratory, the First Affiliated Hospital of Guangxi Medical University, from 2012 to 2014 (n=430;30%≤0.5 mg·L-1; 58.6%= 12 mg·L-1; and 11.2%=2 mg·L-1; 0.2%=4 mg·L-1). RESULTS With increasing vancomycin daily dose, the percentage of patients predicted to achieve AUC0-24/MIC >400 similarly increased. At 35 mg·kg-1·d-1, the percentage predicted to achieve AUC0-24/MIC >400 was 99.41% when MIC was 0.5 mg·L-1. However, the dosage rose to 65 mg·kg-1·d-1 when MIC was 1 mg·L-1. At this regimen, the percentage predicted to achieve AUC0-24/MIC >400 was 97.55%. At a MIC of 2 mg·L-1 and more, none of the dosages predicted to achieve AUC0-24/MIC>400. CONCLUSION Recommended empiric vancomycin dosing in children should be above 35 mg·kg-1·d-1 when MIC is 0.5 mg·L-1. At the MIC is 1 mg·L-1, the recommended regimen should be over 65 mg·kg-1·d-1.

关键词

万古霉素 / 蒙特卡罗模拟 / 药代动力学/药效动力学 / 耐甲氧西林金黄色葡萄球菌 / 儿童

Key words

vancomycin / Monte Carlo simulation / PK/PD / MRSA / children

引用本文

导出引用
张宏亮, 黄振光, 丘岳, 李萌, 刘滔滔. 药代动力学/药效动力学模型结合蒙特卡罗模拟优化儿童耐甲氧西林金黄色葡萄球菌感染的万古霉素给药方案[J]. 中国药学杂志, 2017, 52(3): 217-220 https://doi.org/10.11669/cpj.2017.03.011
ZHANG Hong-liang , HUANG Zhen-guang , QIU Yue, LI Meng, LIU Tao-tao. Optimizing Vancomycin Regimen in Children with MRSA Infections Based on PK/PD Model and Monte Carlo Simulation[J]. Chinese Pharmaceutical Journal, 2017, 52(3): 217-220 https://doi.org/10.11669/cpj.2017.03.011
中图分类号: R969.1   

参考文献


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基金

国家自然科学基金资助项目(81460569);广西卫生厅中医药科技专项(GZZJ13-17);广西高校中青年教师基础能力提升项目(KY2016YB098);广西壮族自治区卫生与计划生育委员会课题(Z2012112)
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