Remdesivir and GS-441524 Extraction by Ex Vivo Extracorporeal Life Support Circuits.
Remdesivir and GS-441524 Extraction by Ex Vivo Extracorporeal Life Support Circuits.
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DOI：
10.1097/mat.0000000000001616
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发表时间：
2022-09-01
期刊：
影响因子：
4.2
通讯作者：
Watt, Kevin M.
中科院分区：
文献类型：
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作者：
Imburgia, Carina E.;Rower, Joseph E.;Green, Danielle J.;Mcknite, Autumn M.;Kelley, Walter E.;Reilly, Christopher A.;Watt, Kevin M.
关键词：
患有严重的COVID相关多器官衰竭的患者通常需要体外生命支持（ECLS），如体外膜肺氧合（ECMO）或连续性肾脏替代治疗（CRRT）。ECLS可以通过多种机制改变药物暴露。Remdesivir（RDV）及其活性代谢物GS-441524可能与ECLS回路相互作用，导致暴露量低于预期。我们评价了闭环、体外ECMO和CRRT回路中的回路-药物相互作用。我们发现ECMO（33.3% [2.0]）和CRRT（3.5% [0.4]）回路中给药后6小时RDV的平均（标准差）回收率较低。这种药物损失似乎主要是由于回路材料对药物的吸附，并可能是由于血液中的代谢。GS-441524在ECMO回路中6小时的回收率较高，为75.8%（16.5），但在CRRT回路中6小时时未检测到。CRRT回路中的损失似乎主要是由于有效的血液透析滤过。这两种分子的损失程度，尤其是在CRRT中，表明在接受ECMO和CRRT支持的患者中，需要调整RDV剂量。
Patients with severe, COVID-related multi-organ failure often require extracorporeal life support (ECLS) such as extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT). ECLS can alter drug exposure via multiple mechanisms. Remdesivir (RDV) and its active metabolite GS-441524 are likely to interact with ECLS circuits, resulting in lower than expected exposures. We evaluated circuit-drug interactions in closed loop, ex vivo ECMO and CRRT circuits. We found that mean (standard deviation) recovery of RDV at 6 hours after dosing was low in both the ECMO (33.3% [2.0]) and CRRT (3.5% [0.4]) circuits. This drug loss appears to be due primarily to drug adsorption by the circuit materials and potentially due to metabolism in the blood. GS-441524 recovery at 6 hours was high in the ECMO circuit 75.8% (16.5), however, was not detectable at 6 hours in the CRRT circuit. Loss in the CRRT circuit appears to be due primarily to efficient hemodiafiltration. The extent of loss for both molecules, especially in CRRT, suggests that in patients supported with ECMO and CRRT, RDV dosing adjustments are needed.