scbmtБИОМЕДИЦИНАJournal Biomed2074-59822713-0428Scientific center of biomedical technologies of Federal Medical and Biological Agencyscbmt-120Research ArticleДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯNON-CLINICAL RESEARCHESЭкспериментальная оценка риска геморрагических осложнений после парентерального введения прямых антикоагулянтных препаратов - дабигатрана этексилата и ривароксабанаExperimental assessment of the risk of hemorrhagic complications following parenteral administration of direct anticoagulants: dabigatran etexilate and rivaroxabanПугачВ. А.PugachV. A.glandula_pinealis@mail.ruТюнинМ. А.TyuninM. A.tuynin84@mail.ruТарасовЕ. А.TarasovE. A.noemail@neicon.ruГоголевскийА. С.GogolevskiyA. S.noemail@neicon.ruСтрокинаЕ. И.StrokinaE. I.noemail@neicon.ruФГБУ «Государственный научно-исследовательский испытательный институт военной медицины» Министерства обороны РоссииRussian Federation201826022019047987Copyright © Пугач В.А., Тюнин М.А., Тарасов Е.А., Гоголевский А.С., Строкина Е.И., 20192019Пугач В.А., Тюнин М.А., Тарасов Е.А., Гоголевский А.С., Строкина Е.И.Pugach V.A., Tyunin M.A., Tarasov E.A., Gogolevskiy A.S., Strokina E.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.scbmt.ru/jour/article/view/120

Исследована эффективность и безопасность дабигатрана этексилата и ривароксабана при их подкожном введении крысам. В качестве препарата сравнения использовали гепарин натрия. Выявлено, что через 2 ч после введения гепарина натрия (250; 500; 1000 ед./кг), дабигатрана этексилата (4,0; 5,0; 7,5; 10,0; 15,0 мг/кг) и ривароксабана (2,5; 5,0; 7,5; 10,0 мг/кг) наступает выраженный антикоагулянтный эффект. Гепарин натрия (в дозе 1000 ед./кг) и ривароксабан (в дозе 10,0 мг/кг) вызывают значительную пролонгацию времени хвостового кровотечения и критическое увеличение показателей коагуляционного гемостаза. При определении широты терапевтического действия исследуемых препаратов установлено, что дабигатрана этексилат имеет большую терапевтическую широту, чем гепарин натрия и ривароксабан. Результаты исследования могут служить обоснованием возможности разработки инъекционной лекарственной формы дабигатрана этексилата и могут быть использованы для совершенствования терапии критических состояний с высоким риском развития синдрома диссеминированного внутрисосудистого свертывания в условиях чрезвычайных ситуаций и вооруженных конфликтов.

We investigated the efficacy and safety of dabigatran etexilate and rivaroxaban after subcutaneous administration to rats. Heparin sodium was used as a reference drug. It was revealed that 2 hours following heparin sodium administration (250; 500; 1000 U/kg), dabigatran etexilate (4,0; 5,0; 7,5; 10,0; 15,0 mg/kg) and rivaroxaban (2,5; 5,0; 7,5; 10,0 mg/kg) have pronounced anticoagulant effect. Heparin sodium (1000 U/kg) and rivaroxaban (10,0 mg/kg) caused a significant prolongation of rat tail bleeding time and a critical increase in parameters of blood coagulation. Dabigatran etexilate was shown to be of higher therapeutical possibility than heparin sodium and rivaroxaban. Our results can justify the development of injectable dosage form of dabigatran etexilate. It may be important to improve the treatment of critical states with high risk of disseminated intravascular coagulation in emergency and military conflicts.

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The authors declare that there are no conflicts of interest present.