Temple University, Philadelphia, PA, USA.
Mass Spectrometry Facility, University of Massachusetts Medical School, Shrewsbury, MA, USA.
Drugs R D. 2020 Sep;20(3):217-223. doi: 10.1007/s40268-020-00308-1.
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.
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.
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.
Sorbent-mediated technology may represent a viable pathway for edoxaban removal from human plasma or albumin solution.
基于之前在吸附剂介导的替卡格雷洛、达比加群和造影剂清除方面的经验,我们在这项研究中测试了两种吸附剂对新型直接口服抗凝药(factor Xa antagonist direct oral anticoagulant)依度沙班清除效果。
我们在使用人血浆和 4%牛血清白蛋白溶液作为药物载体的实验中,让 100mL 依度沙班溶液在六个第一通过周期中循环通过 40mL 吸附柱(三次循环通过 CytoSorb,剩余三次循环通过 Porapak Q 50-80 目)。药物浓度通过液相色谱-串联质谱法进行测量。
在两项用人血浆进行的实验中,CytoSorb 或 Porapak Q 50-80 目使依度沙班浓度分别从 276.8ng/mL 降至 2.7ng/mL 和检测不到的浓度(p=0.0031)。依度沙班浓度从 407ng/mL±216ng/mL 降至 3.3ng/mL±7ng/mL(p=0.017),在所有 6 个人血浆样本(两个样本)和牛血清白蛋白溶液样本(四个样本)中,平均清除率为 99%。在 6 个吸附样本中的 4 个样本中,药物浓度检测不到。
吸附介导技术可能是从人血浆或白蛋白溶液中清除依度沙班的可行途径。