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不同血液滤过器对利奈唑胺和多利培南清除率的体外评价。

In vitro Evaluation of Linezolid and Doripenem Clearance with Different Hemofilters.

机构信息

Department of Anesthesiology and Clinical Care Medicine, Fujita Health University School of Medicine, Toyoake, Japan.

Laboratory for Immune Response and Regulatory Medicine, Fujita Health University School of Medicine, Toyoake, Japan,

出版信息

Blood Purif. 2020;49(3):295-301. doi: 10.1159/000504039. Epub 2020 Jan 29.

Abstract

INTRODUCTION

Renal replacement therapy (RRT) is widely used in the treatment of septic acute kidney injury. However, little is known about how the adsorption properties of hemofilters used in RRT affect antibiotic concentration. Because a cytokine-adsorption membrane is frequently used in RRT, it is important to determine the antibiotic adsorption capacity of this membrane.

OBJECTIVE

The present study aimed to investigate the antibiotic adsorption capacity of different hemofilter membranes by in vitro experiments using 2 antibacterial agents (linezolid and doripenem).

METHODS

We performed experimental hemofiltration in vitro using polyacrylonitrile (AN69ST), polymethylmethacrylate (PMMA), and polysulfone (PS) hemofilters for 1,440 min. The test solution was a 1,000-mL substitution fluid containing 30 µg/mL linezolid and 120 µg/mL doripenem. We measured drug concentrations at the inlet, outlet, and filtrate ports of the hemofilters for 1,440 min and calculated the sieving coefficient (SC) and adsorption rate (Ra) of the drugs onto the hemofilters.

RESULTS

The amount of linezolid adsorbed onto AN69ST, PMMA, and PS membranes was decreased relative to that in the control group at 15 min (p < 0.05). However, no SC for linezolid was obtained thereafter. The Ra of linezolid onto AN69ST, PMMA, and PS membranes was higher than that in the control group (p < 0.05). In contrast, no significant differences were observed in the concentrations and Ra values of doripenem adsorbed onto AN69ST, PMMA, and PS membranes compared with those in the control group.

CONCLUSIONS

Doripenem was not adsorbed onto PMMA, PS, and AN69ST membranes. Linezolid was adsorbed onto PMMA, PS, and AN69ST membranes, but only temporarily, and this did not affect drug bioavailability.

摘要

简介

肾脏替代疗法(RRT)在治疗脓毒症急性肾损伤中被广泛应用。然而,人们对于 RRT 中使用的血液滤过器的吸附特性如何影响抗生素浓度知之甚少。由于在 RRT 中经常使用细胞因子吸附膜,因此确定该膜的抗生素吸附能力非常重要。

目的

本研究旨在通过使用 2 种抗菌药物(利奈唑胺和多利培南)的体外实验,研究不同血液滤过器膜的抗生素吸附能力。

方法

我们使用聚丙烯腈(AN69ST)、聚甲基丙烯酸甲酯(PMMA)和聚砜(PS)血液滤过器进行了 1440 分钟的体外实验。测试溶液为含有 30μg/mL 利奈唑胺和 120μg/mL 多利培南的 1000mL 替代液。我们在 1440 分钟内测量了血液滤过器的进口、出口和滤液端口的药物浓度,并计算了药物对血液滤过器的筛系数(SC)和吸附率(Ra)。

结果

与对照组相比,利奈唑胺在 15 分钟时被吸附到 AN69ST、PMMA 和 PS 膜上的量减少(p < 0.05)。然而,此后并未获得利奈唑胺的 SC。利奈唑胺在 AN69ST、PMMA 和 PS 膜上的 Ra 高于对照组(p < 0.05)。相反,与对照组相比,利奈唑胺在 AN69ST、PMMA 和 PS 膜上的浓度和 Ra 值没有明显差异。

结论

多利培南未被 PMMA、PS 和 AN69ST 膜吸附。利奈唑胺被 PMMA、PS 和 AN69ST 膜吸附,但只是暂时的,这不会影响药物的生物利用度。

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