持续低效率透析的危重病人中粘菌素的处置:一项人群药代动力学研究。

IF 10.9 1区 医学 Q1 INFECTIOUS DISEASES
Adhiratha Boonyasiri, Dominika T Fuhs, Thummaporn Naorungroj, Lu Wang, Jiping Wang, Ranistha Ratanarat, Jian Li, Roger L Nation, Visanu Thamlikitkul, Cornelia B Landersdorfer
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引用次数: 0

摘要

目的:虽然粘菌素(以甲磺酸粘菌素[CMS]的形式给药)被用于治疗接受持续低效率透析(SLED)的危重患者的感染,但关于适当的给药方案的信息缺乏。本研究旨在表征多粘菌素在SLED期间的群体药代动力学(popPK),并评估不同方案的抗菌益处和多粘菌素肾毒性的可能性。方法:前瞻性popPK研究纳入13例危重患者(6例女性),采用CMS和SLED (6-8h)治疗。每个受试者在非SLED日和SLED日分别研究形成的粘菌素的PK(在SLED日先研究n=8)。在非sled日给予单次静脉注射剂量[150mg粘菌素碱活性(CBA)]。在一个SLED日,患者每12小时接受150mg CBA。在这两天的24小时内,连续采集血液、尿液和透析液样本。高效液相色谱法测定粘菌素血浆浓度。进行了PopPK建模和蒙特卡罗仿真。结果:线性单室配置模型很好地描述了数据。人群平均表观粘菌素清除率(不包括SLED清除率)为1.69 L/h(20%个体间变异性[iv], 42.1%场合间变异性)。表观粘菌素SLED清除率为3.49 L/h (41.7% iv),占SLED日总粘菌素清除率的67.4%。表观分布容积为50.2 L(23.0%)。结论:在SLED期间粘菌素清除率明显较高;因此,在CMS给药方案中应该考虑到SLED。该项目产生了临床适用的方案,包括负荷剂量,以达到接受SLED患者所需的目标实现概率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Disposition of colistin in critically-ill patients on sustained low-efficiency dialysis: A population pharmacokinetic study.

Objectives: Although colistin (administered as colistin methanesulphonate [CMS]) is used to treat infections in critically-ill patients undergoing sustained low-efficiency dialysis (SLED), there is a paucity of information on appropriate dosing regimens. This study aimed to characterize the population pharmacokinetics (popPK) of colistin during SLED and evaluate the likelihood of antibacterial benefit and colistin nephrotoxicity for different regimens.

Methods: A prospective popPK study included 13 critically-ill patients (six females) treated with CMS and receiving SLED (6-8 hours). For each subject, the PK of formed colistin was studied on a non-SLED day and a SLED day (n = 8 studied during SLED day first). A single intravenous daily dose (150 mg colistin base activity) was administered on a non-SLED day. On a SLED day, patients received 150 mg colistin base activity 12-hourly. Serial blood, urine and dialysate samples were collected over 24 hours on both days. Colistin plasma concentrations were measured by high-performance liquid chromatography. PopPK modelling and Monte Carlo simulations were performed.

Results: A linear one-compartment disposition model well-described the data. The population mean apparent colistin body clearance, excluding SLED clearance, was 1.69 L/h (20.6% inter-individual variability [IIV], 42.1% inter-occasion variability). The apparent colistin SLED clearance was 3.49 L/h (41.7% IIV), i.e. 67.4% of total colistin clearance on a SLED day. The apparent volume of distribution was 50.2 L (23.0% IIV).

Discussion: Colistin clearance was substantially higher during SLED; therefore, SLED should be accounted for in CMS dosing regimens. This project generated clinically applicable regimens, such as loading doses, to achieve required probabilities of target attainment in patients undergoing SLED.

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来源期刊
CiteScore
25.30
自引率
2.10%
发文量
441
审稿时长
2-4 weeks
期刊介绍: Clinical Microbiology and Infection (CMI) is a monthly journal published by the European Society of Clinical Microbiology and Infectious Diseases. It focuses on peer-reviewed papers covering basic and applied research in microbiology, infectious diseases, virology, parasitology, immunology, and epidemiology as they relate to therapy and diagnostics.
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