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

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

Paul Biever  1   2   3 , Dawid L Staudacher  1   2 , Michaela J Sommer  4   5 , Hannah Triebel  4 , Merja A Neukamm  4 , Christoph Bode  1   2 , Alexander Supady  1   2   6 , Achim Lother  1   2   7
Affiliations

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

Paul Biever et al. Pharmacol Res Perspect. 2021 Apr.

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.

Keywords: COVID-19; SARS-CoV-2; cytokine; hemoadsorption; remdesivir.

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Conflict of interest statement

Paul Biever and Alexander Supady received speakers' honoraria from CytoSorbents, the manufacturer of the CytoSorb® device. The Department of Cardiology and Angiology I received a research grant from CytoSorbents not related to the present study.

Figures

FIGURE 1
FIGURE 1
Experimental setup. A CytoSorb® device was integrated in a custom‐made system, and serum containing remdesivir or GS‐441524, respectively, was circulated from a reservoir at a flow rate of 200 mL/min. Samples were taken from the circuit before (pre) and after (post) the adsorber device at 0, 5, 10, 15, 30, and 60 minutes for quantification of remdesivir or GS‐441524
FIGURE 2
FIGURE 2
Adsorption of remdesivir or GS‐441524 in vitro. Concentrations of remdesivir or GS‐441524 in samples taken from the circuit before (pre) and after (post) the adsorber device were quantified by liquid chromatography with mass spectrometry detection. Dashed lines indicate calculated half‐life (t1/2)
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References

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