依唑康唑在危重患者体外膜氧合支持中的药代动力学:一个病例系列。

IF 4.3 2区 医学 Q1 INFECTIOUS DISEASES
Laura Doménech-Moral, Sonia García-García, Alba Pau-Parra, Manuel Sosa, Adrian Puertas Sanjuan, Camilo Bonilla, Elisabeth Gallart, Laura Castellote, Patricia Faixó, Jessica Guevara, Albert Vilanova, María Martínez-Pla, Aldair Conto, Xavier Nuvials, Pilar Lalueza, Ricard Ferrer, Maria Queralt Gorgas, Jordi Riera
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引用次数: 0

摘要

背景/目的:体外膜氧合(ECMO)越来越多地用于危重患者,但可能显著改变抗真菌药物的药代动力学(PK)。ECMO患者血浆Isavuconazole (IsaPlasm)浓度数据有限。我们的目的是评估接受ECMO的COVID-19危重患者的异唑康唑暴露和变异性。方法:对采用静脉-静脉ECMO进行呼吸支持的危重患者进行依舒康唑的药代动力学分析。采用治疗药物监测(TDM)在多个时间点测量血浆浓度,包括膜氧合器前后的采样。估计PK参数-曲线下面积(AUC0-24),最小血浆浓度(Cmin),消除半衰期(T1/2),分布体积(Vd)和清除率(CL)-并与非ecmo人群的已发表数据进行比较。结果:纳入5例患者。中位AUC0-24为227.3µg·h/mL (IQR 182.4-311.35),高于非ecmo患者的报告。中位Vd为761 L(727-832),提示在ECMO回路中有广泛的外周分布和潜在的药物隔离。CL升高1.6 L/h, IQR 1.5 ~ 3.4。最近更换ECMO电路的两名患者表现出明显的跨膜药物损失。肥胖和低白蛋白血症被确定为与药物暴露改变相关的因素。结论:依唑康唑药代动力学在ECMO危重患者中表现出明显的变异性。AUC和Vd的增加,以及清除率的降低,突出了个体化给药的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Pharmacokinetics of Isavuconazole During Extracorporeal Membrane Oxygenation Support in Critically Ill Patients: A Case Series.

Background/objectives: Extracorporeal membrane oxygenation (ECMO) is increasingly used in critically ill patients, but may significantly alter the pharmacokinetics (PK) of antifungals. Data on plasma concentrations of Isavuconazole (IsaPlasm) in ECMO patients are limited. Our objective is to evaluate Isavuconazole exposure and variability in critically ill COVID-19 patients receiving ECMO.

Methods: We conducted a pharmacokinetic analysis of Isavuconazole in critically ill patients receiving Veno-Venous ECMO for respiratory support. Plasma concentrations were measured using therapeutic drug monitoring (TDM) at multiple time points, including sampling before and after the membrane oxygenator. PK parameters-Area Under Curve (AUC0-24), Minimum Plasma Concentration (Cmin), Elimination Half-Life (T1/2), volume of distribution (Vd), and clearance (CL)-were estimated and compared with published data in non-ECMO populations.

Results: Five patients were included. The median AUC0-24 was 227.3 µg·h/mL (IQR 182.4-311.35), higher than reported in non-ECMO patients. The median Vd was 761 L (727-832), suggesting extensive peripheral distribution and potential drug sequestration in the ECMO circuit. CL was increased (1.6 L/h, IQR 1.5-3.4). Two patients with recently replaced ECMO circuits exhibited significant drug loss across the membrane. Obesity and hypoalbuminemia were identified as factors associated with altered drug exposure.

Conclusions: Isavuconazole pharmacokinetics show marked variability in critically ill ECMO patients. Increased AUC and Vd, along with reduced clearance, highlight the need for individualized dosing.

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来源期刊
Antibiotics-Basel
Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics
CiteScore
7.30
自引率
14.60%
发文量
1547
审稿时长
11 weeks
期刊介绍: Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.
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