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血液吸附从循环中清除瑞德西韦:对 COVID-19 治疗的影响。

Hemoadsorption eliminates remdesivir from the circulation: Implications for the treatment of COVID-19.

机构信息

Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

出版信息

Pharmacol Res Perspect. 2021 Apr;9(2):e00743. doi: 10.1002/prp2.743.

Abstract

Both antiviral treatment with remdesivir and hemoadsorption using a CytoSorb adsorption device are applied in the treatment of severe COVID-19. The CytoSorb adsorber consists of porous polymer beads that adsorb a broad range of molecules, including cytokines but also several therapeutic drugs. In this study, we evaluated whether remdesivir and its main active metabolite GS-441524 would be adsorbed by CytoSorb . Serum containing remdesivir or GS-441524 was circulated in a custom-made system containing a CytoSorb device. Concentrations of remdesivir and GS-441524 before and after the adsorber were analyzed by liquid chromatography-tandem mass spectrometry. Measurements of remdesivir in the outgoing tube after the adsorber indicated almost complete removal of remdesivir by the device. In the reservoir, concentration of remdesivir showed an exponential decay and was not longer detectable after 60 mins. GS-441524 showed a similar exponential decay but, unlike remdesivir, it reached an adsorption-desorption equilibrium at ~48 µg/L. Remdesivir and its main active metabolite GS-441524 are rapidly eliminated from the perfusate by the CytoSorb adsorber device in vitro. This should be considered in patients for whom both therapies are indicated, and simultaneous application should be avoided. In general, plasma levels of therapeutic drugs should be closely monitored under concurrent CytoSorb therapy.

摘要

瑞德西韦的抗病毒治疗和使用 CytoSorb 吸附装置的血液吸附都应用于严重 COVID-19 的治疗。CytoSorb 吸附剂由多孔聚合物珠粒组成,可吸附包括细胞因子在内的多种分子,但也包括几种治疗药物。在这项研究中,我们评估了瑞德西韦及其主要活性代谢物 GS-441524 是否会被 CytoSorb 吸附。含有瑞德西韦或 GS-441524 的血清在包含 CytoSorb 装置的定制系统中循环。使用液相色谱-串联质谱法分析吸附前后瑞德西韦和 GS-441524 的浓度。在吸附器后的输出管中测量瑞德西韦表明,该装置几乎完全去除了瑞德西韦。在储液器中,瑞德西韦的浓度呈指数衰减,60 分钟后不再检测到。GS-441524 也表现出类似的指数衰减,但与瑞德西韦不同,它在约 48μg/L 处达到吸附-解吸平衡。瑞德西韦及其主要活性代谢物 GS-441524 可在体外通过 CytoSorb 吸附器迅速从灌流液中消除。在同时需要这两种治疗的患者中应考虑到这一点,应避免同时应用。一般来说,在同时进行 CytoSorb 治疗时,应密切监测治疗药物的血浆水平。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3541/7953359/957a40d4afea/PRP2-9-e00743-g001.jpg

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