Scavenging effect of DOAC-Stop on zifaxaban <italic style="font-style: italic">in vitro</italic> and <italic style="font-style: italic">in vivo</italic>

Sipei ZHANG; Yanwen ZHANG; Shuangyong SUN

doi:10.16016/j.1000-5404.202101080

您当前的位置：

首页 >

文章列表页 >

Scavenging effect of DOAC-Stop on zifaxaban in vitro and in vivo

Pharmacy | 更新时间：2026-01-09

- Scavenging effect of DOAC-Stop on zifaxaban in vitro and in vivo
- Journal of Third Military Medical University Vol. 43, Issue 13, Pages: 1293-1298(2021)
- 作者机构：
  
  1.300222 天津，天津市胸科医院药剂科
  2.300070 天津，天津医科大学研究生院
  3.300193 天津，天津医药集团研究院有限公司
- 作者简介：
- 基金信息：
  
  the Second Batch of Special Plan for Young Top-Notch Talents Foundation of Tianjin(TJTZJH-QNBJRC-2-7)
- DOI：10.16016/j.1000-5404.202101080
  CLC： R965;R969.2;R973.2
- Received：08 January 2021，
  
  Revised：2021-03-24，
  
  Published：15 July 2021
- 稿件说明：
移动端阅览
Sipei ZHANG, Yanwen ZHANG, Shuangyong SUN. Scavenging effect of DOAC-Stop on zifaxaban in vitro and in vivo[J]. Journal of Third Military Medical University, 2021, 43(13): 1293-1298.
DOI：

Sipei ZHANG, Yanwen ZHANG, Shuangyong SUN. Scavenging effect of DOAC-Stop on zifaxaban in vitro and in vivo[J]. Journal of Third Military Medical University, 2021, 43(13): 1293-1298. DOI： 10.16016/j.1000-5404.202101080.

摘要

目的

观察DOAC-Stop对血浆内知非沙班的清除作用。

方法

离体实验中，犬血浆内加入0.1 mg/mL的知非沙班致凝血酶原时间(prothrombin time

PT)、活化部分凝血酶时间(activated partial thrombopastin time

APTT)延长，凝血因子Xa(FXa)活性降低，然后加入梯度浓度(1/512~1 minitabs)的DOAC-Stop，观察血浆PT、APTT、FXa活性以及知非沙班浓度变化情况；在体实验中，大鼠灌胃给予30 mg/kg的知非沙班，1.5 h后取血分离血浆，使用DOAC-Stop处理后，观察血浆PT、APTT、FXa活性及知非沙班浓度变化情况。

结果

在加入0.1 mg/mL知非沙班的血浆内加入梯度浓度的DOAC-Stop后，PT、APTT显著缩短(

0.001)，FXa活性升高(

0.001)，知非沙班浓度显著降低(

0.001)，且具有一定的剂量依赖性。灌胃给予30 mg/kg知非沙班大鼠的血浆使用DOAC-Stop处理后，PT、APTT显著降低(

0.001)，FXa活性恢复(

0.001)，血浆内无知非沙班检出，各项指标已接近对照组。

结论

DOAC-Stop对血浆内知非沙班具有良好的清除作用。

Abstract

Objective

To determine the scavenging effect of DOAC-Stop on zifaxaban in plasma.

Methods

in vitro

experiment

0.1 mg/mL zifaxaban was added into the plasma derived from Beagle dogs

then

DOAC-Stop with gradient concentration (1/512~1 minitabs) was added to observe the changes of prothrombin time (PT)

activated partial thrombopastin time (APTT)

FXa activity and zifaxaban concentration. In

in vivo

experiment

Wistar rats of both sexes were given 30 mg/kg zifaxaban

by gavage

and in 1.5 h later

their blood samples were harvested to separate plasma. The plasma was treated with DOAC-Stop

and PT

APTT

FXa activity and zifaxaban concentration in the plasma were measured.

Results

The results of

in vitro

experiments showed that when the gradient concentrations of DOAC-Stop were added to the plasma containing 0.1 mg/mL zifaxaban

PT and APTT were significantly shortened (

0.001)

FXa activity was increased (

0.001)

and concentration of zifaxaban was significantly decreased (

0.001)

in a dose-dependent manner. After the plasma from zifaxaban gavaged rats was treated with DOAC-Stop

PT and APTT were significantly shortened (

0.001)

FXa activity was restored (

0.001)

and no zifaxaban was detected in the plasma

which indicated that all indexes in the DOAC-Stop group were close to those of the blank control group.

Conclusion

DOAC-Stop has a good scavenging effect on zifaxaban in plasma.

关键词

Keywords

references

YEH C H, FREDENBURGH J C, WEITZ J I. Oral direct factor Xa inhibitors[J]. Circ Res, 2012, 111(8): 1069-1078. DOI:10.1161/CIRCRESAHA.112.276741.

MACKMAN N, BERGMEIER W, STOUFFER G A, et al . Therapeutic strategies for thrombosis: new targets and approaches[J ] . Nat Rev Drug Discov, 2020, 19(5): 333-352. DOI:10.1038/s41573-020-0061-0.

QIU X M, ZHOU J J, WANG W T, et al . Effect of a new inhibitor of factor Xa zifaxaban, on thrombosis in the inferior vena cava in rabbits[J ] . J Thromb Thrombolysis, 2019, 47(1): 80-86. DOI:10.1007/s11239-018-1743-x.

QIU X M, WANG W T, ZHAO Z Y, et al . Pre-clinical pharmacodynamic study of a novel oral factor Xa inhibitor zifaxaban[J ] . Eur J Pharmacol, 2018, 836: 50-56. DOI:10.1016/j.ejphar.2018.08.019.

IWATSUKI Y, SATO T, MORITANI Y, et al . Biochemical and pharmacological profile of darexaban, an oral direct factor Xa inhibitor[J ] . Eur J Pharmacol, 2011, 673(1/2/3): 49-55. DOI:10.1016/j.ejphar.2011.10.009.

HU X, XIAO Y, YU C, et al . Characterization of a novel s elective factor Xa inhibitor, DJT06001, which reduces Thrombus formation with low risk of bleeding[J ] . Eur J Pharmacol, 2018, 825: 85-91. DOI:10.1016/j.ejphar.2018.02.031.

HE K, LUETTGEN J M, ZHANG D, et al . Preclinical pharmacokinetics and pharmacodynamics of apixaban, a potent and selective factor Xa inhibitor[J ] . Eur J Drug Metab Pharmacokinet, 2011, 36(3): 129-139. DOI:10.1007/s13318-011-0037-x.

RODRIGUES A O, DAVID C, FERREIRA J J, et al . The incidence of thrombotic events with idarucizumab and andexanet alfa: a systematic review and meta-analysis[J ] . Thromb Res, 2020, 196: 291-296. DOI:10.1016/j.thromres.2020.09.003.

RAWAL A, ARDESHNA D, MINHAS S, et al . Current status of oral anticoagulant reversal strategies: a review[J ] . Ann Transl Med, 2019, 7(17): 411. DOI:10.21037/atm.2019.07.101.

KAATZ S, BHANSALI H, GIBBS J, et al . Reversing factor Xa inhibitors—clinical utility of andexanet alfa[J ] . J Blood Med, 2017, 8: 141-149. DOI:10.2147/jbm.s121550.

NAFEE T, ASLAM A, CHI G, et al . Andexanet Alfa for the reversal of anticoagulant activi ty in patients treated with direct and indirect factor Xa inhibitors[J ] . Expert Rev Cardiovasc Ther, 2017, 15(4): 237-245. DOI:10.1080/14779072.2017.1305889.

ALMEGREN M. Reversal of direct oral anticoagulants[J]. Vasc Health Risk Manag, 2017, 13: 287-292. DOI:10.2147/vhrm.s138890.

EXNER T, MICHALOPOULOS N, PEARCE J, et al . Simple method for removing DOACs from plasma samples[J ] . Thromb Res, 2018, 163: 117-122. DOI:10.1016/j.thromres.2018.01.047.

EXNER T, AHUJA M, ELLWOOD L. Effect of an activated charcoal product (DOAC Stop TM ) intended for extracting DOACs on various other APTT-prolonging anticoagulants[J ] . Clin Chem Lab Med, 2019, 57(5): 690-696. DOI:10.1515/cclm-2018-0967.

FAVRESSE J, LARDINOIS B, SABOR L, et al . Evaluation of the DOAC-stop Ⓡ procedure to overcome the effect of DOACs on several thrombophilia screening tests[J ] . TH Open, 2018, 2(2): e202-e209. DOI:10.1055/s-0038-1657785..

JACQUEMIN M, TOELEN J, FEYEN L, et al . The adsorption of dabigatran is as efficient as addition of idarucizumab to neutralize the drug in routine coagulation assays[J ] . Int J Lab Hematol, 2018, 40(4): 442-447. DOI:10.1111/ijlh.12807.

EXNER T, RIGANO J, FAVALORO E J. The effect of DOACs on laboratory tests and their removal by activated carbon to limit interference in functional assays[J]. Int J Lab Hematol, 2020, 42(Suppl 1): 41-48. DOI:10.1111/ijlh.13196.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Expression and diagnostic significance of lncRNA NEAT1 in peripheral blood of patients with non-small cell lung cancer

Determination of ginsenoside Rg3 in rat plasma using high-performance liquid chromatography-tandem mass spectrometry

Change and clinical significance of plasma circulating DNA levels in burn patients

Determination and pharmacokinetic study of honokiol in rat plasma by RP-HPLC

Comparative proteomic analysis of plasma from euthymic bipolar disorder patients and healthy controls

Related Author

Yafei LI

Xiaoping GUO

Ying XIANG

Shuai YUAN

Long WU

Na WU

Chengying LI

Bin XU

Related Institution

Department of Epidemiology, School of Public Health, Guizhou Medical University

Department of Epidemiology, Faculty of Military Preventive Medicine, Army Medical University(Third Military Medical University)

Department of Thoracic Surgery, Second Affiliated Hospital, Army Medical University(Third Military Medical University)

Institute of Respiratory Diseases, Key Laboratory of Respiratory Diseases, Second Affiliated Hospital, Army Medical University(Third Military Medical University)

Department of Pharmacy, First Affiliated Hospital, Army Medical University (Third Military Medical University)

⁰

Scavenging effect of DOAC-Stop on zifaxaban in vitro and in vivo

DOI：10.16016/j.1000-5404.202101080

摘要

Abstract

关键词

Keywords

references