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米卡芬净群体药代动力学模型的评估:对危重症患者给药方案优化的意义

Evaluation of Population Pharmacokinetic Models of Micafungin: Implications for Dosing Regimen Optimization in Critically Ill Patients.

作者信息

Li Xiping, Liu Xiaoqin, Mao Juehui, Liu Dong, Jiao Zheng

机构信息

Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China.

出版信息

Pharmaceutics. 2024 Aug 29;16(9):1145. doi: 10.3390/pharmaceutics16091145.

Abstract

Micafungin (MFG) is a widely used echinocandin antifungal agent for treating invasive candidiasis, particularly in critically ill patients. However, its pharmacokinetics can be highly variable in this population. This systematic review aims to summarize population pharmacokinetic models and provide recommendations for its use in intensive care unit (ICU) patients. Monte Carlo simulations were implemented to compare pharmacokinetic parameters and probability of target attainment (PTA) against various species. A total of 16 studies were included, of which 6 studies were conducted in adult ICU patients. The key covariates were body size, liver function, and sepsis-related organ failure assessment score (SOFA) score. The median MFG clearance in adult ICU patients was 30-51% higher than in adult non-ICU patients. For infections with with MIC below 0.016 mg/L, micafungin dosages of 100 and 150 mg/d were recommended for adult non-ICU and ICU patients, respectively. For and , 200 and 250 mg/d were recommended, respectively. However, for and , none of the tested dosage regimens achieved assumed PTA criteria within MIC ranges of 0.125-0.25 mg/L and 0.125-2 mg/L, respectively. Therefore, MFG dosage regimens in ICU and non-ICU patients should be tailored based on the spp. and their respective MIC values.

摘要

米卡芬净(MFG)是一种广泛用于治疗侵袭性念珠菌病的棘白菌素类抗真菌药物,尤其适用于重症患者。然而,其在该人群中的药代动力学可能具有高度变异性。本系统评价旨在总结群体药代动力学模型,并为其在重症监护病房(ICU)患者中的应用提供建议。实施蒙特卡洛模拟以比较药代动力学参数和不同菌种的达标概率(PTA)。共纳入16项研究,其中6项研究在成年ICU患者中进行。关键协变量为体型、肝功能和脓毒症相关器官功能衰竭评估评分(SOFA)。成年ICU患者米卡芬净的清除率中位数比成年非ICU患者高30%-51%。对于最低抑菌浓度(MIC)低于0.016 mg/L的感染,推荐成年非ICU和ICU患者米卡芬净剂量分别为100和150 mg/d。对于MIC为0.016-0.125 mg/L和0.125-0.25 mg/L的情况,推荐剂量分别为200和250 mg/d。然而,对于MIC为0.125-0.25 mg/L和0.125-2 mg/L的情况,分别没有任何测试的给药方案在相应MIC范围内达到假定的PTA标准。因此,ICU和非ICU患者的米卡芬净给药方案应根据念珠菌属菌种及其各自的MIC值进行调整。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c182/11434802/072541863731/pharmaceutics-16-01145-g001.jpg

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