In-Vitro Sorbent-Mediated Removal of Edoxaban from Human Plasma and Albumin Solution

Abstract

Background and Objective Based on previous experience of sorbent-mediated ticagrelor, dabigatran, and radiocontrast agent removal, we set out in this study to test the effect of two sorbents on the removal of edoxaban, a factor Xa antagonist direct oral anticoagulant. Methods We circulated 100 mL of edoxaban solution during six first-pass cycles through 40-mL sorbent columns (containing either CytoSorb in three passes or Porapak Q 50–80 mesh in the remaining three passes) during experiments using human plasma and 4% bovine serum albumin solution as drug vehicles. Drug concentration was measured by liquid chromatography-tandem mass spectrometry. Results Edoxaban concentration in two experiments performed with human plasma dropped from 276.8 to 2.7 ng/mL and undetectable concentrations, respectively, with CytoSorb or Porapak Q 50–80 mesh ( p = 0.0031). The average edoxaban concentration decreased from 407 ng/mL ± 216 ng/mL to 3.3 ng/mL ± 7 ng/mL ( p = 0.017), for a removal rate of 99% across all six samples of human plasma (two samples) and bovine serum albumin solution (four samples). In four out of the six adsorbed samples, the drug concentrations were undetectable. Conclusion Sorbent-mediated technology may represent a viable pathway for edoxaban removal from human plasma or albumin solution. Electronic supplementary material The online version of this article (10.1007/s40268-020-00308-1) contains supplementary material, which is available to authorized users.

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

“…Our data suggest that concurrent use of remdesivir and hemoadsorption should rather be avoided and support the view that sequential use at different stages of COVID‐19 may be preferred. The results presented here complement previous reports describing desired or unwanted adsorption of various molecules by the CytoSorb ® device 7,8,12‐15 . In vitro data are available on a broad range of therapeutic drugs that are commonly used in intensive care medicine (Table 1).…”

“…The results presented here complement previous reports describing desired or unwanted adsorption of various molecules by the CytoSorb ® device. 7,8,[12][13][14][15] In vitro data are available on a broad range of therapeutic drugs that are commonly used in intensive care medicine (Table 1). Drugs that are adsorbed differ in molecule size, solubility, and protein binding, making it difficult to make predictions about a particular substance.…”

A New Tool in the Management of Direct-Acting Oral Anticoagulants in Emergency Cardiac Surgery

“…15,16 However, clinical data on the efficacy of CytoSorb ® HA to reduce relevant levels of direct Xa inhibitors in patients undergoing emergent cardiac surgery are limited to case reports and small case series. 14,[17][18][19]30 The in vitro study by Røed-Undlien and colleagues supports these preliminary clinical data. 9 The present study shows that CytoSorb ® HA seems to be able to remove relevant amounts of DOACs from reconstituted whole blood.…”

“…Finally, the use of the CytoSorb ® HA during CPB has been suggested to reduce plasma DOAC levels in case reports and small case series from different European centers. [14][15][16][17][18][19] Recently, this system received the full FDA investigational device exemption (ICE) approval to be used for DOAC removal in urgent cardiac surgery.…”

Extracorporeal haemoadsorption: does the evidence support its routine use in critical care?

“…Therefore, in our view, routine use of haemoadsorption in these conditions cannot be recommended at this time. 40,41 The pathophysiological and molecular basis for the proposed effect of haemoadsorption has also not been adequately demonstrated in clinical studies. In RCTs published to date, haemoadsorption has not reliably been Schematic representation of elevated and assumed concentration-dependent toxic effects of cytokines and other inflammatory mediators (left), which might be mitigated by the reduction of particularly elevated peak concentrations via haemoadsorption 22,23 to restore the physiological balance of these mediators (right).…”