From the Department of Pediatrics, University of Utah, Salt Lake City, Utah.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah.
ASAIO J. 2022 Sep 1;68(9):1204-1210. doi: 10.1097/MAT.0000000000001616. Epub 2021 Nov 17.
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). An 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.
患有严重 COVID 相关多器官衰竭的患者通常需要体外生命支持 (ECLS)，如体外膜氧合 (ECMO) 或持续肾脏替代疗法 (CRRT)。ECLS 可以通过多种机制改变药物暴露。瑞德西韦 (RDV) 和其活性代谢物 GS-441524 可能与 ECLS 回路相互作用，导致暴露水平低于预期。我们评估了闭环、离体 ECMO 和 CRRT 回路中的回路-药物相互作用。我们发现，在 ECMO（33.3%[2.0]）和 CRRT（3.5%[0.4]）回路中，给药后 6 小时 RDV 的平均（标准偏差）回收率均较低。这种药物损失似乎主要是由于回路材料对药物的吸附，并且可能是由于血液中的代谢。GS-441524 在 ECMO 回路中的回收率在 6 小时时很高，为 75.8%（16.5）；然而，在 CRRT 回路中，6 小时时无法检测到。CRRT 回路中的损失似乎主要是由于高效血液透析滤过。这两种分子的损失程度，特别是在 CRRT 中，表明在接受 ECMO 和 CRRT 支持的患者中，需要调整 RDV 的剂量。
