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.

Fig. 1

Experimental set-up

Fig. 2

Concentration of edoxaban in the six samples of human plasma (two samples) and bovine serum albumin (BSA) solution (four samples) as measured by liquid chromatography-tandem mass spectrometry before (baseline concentration) and after sorbent adsorption (adsorbed concentration) (a); average concentration of edoxaban in human plasma before and after sorbent adsorption (b)

Fig. 3

Average removal rate of edoxaban across all six samples (a), in human plasma [two samples (b)] and comparatively CytoSorb for three samples and Porapak Q 50–80 mesh column for the remaining three samples (c)