活化X因子的口服活性合成对手在非人类灵长类动物中的抗血栓作用
T Yokoyama1, A B Kelly, U M Marzec
1Division of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Circulation
|August 1, 1995
概括
一种口服的XA因子抑制剂,APAP,通过非活化FXa,有效地减少了静脉类型血栓的形成. 然而,它没有影响动脉类型的血栓,这表明有针对性的抗血栓潜力.
科学领域:
- 药理学 药理学是指药理学的学科.
- 血液静止和血栓形成
背景情况:
- 激活的XA因子 (FXa) 在血液静止和血栓形成中起着关键作用.
- FXa是开发抗血栓治疗的关键目标.
研究的目的:
- 为了评估口服FXa抑制剂,APAP在的抗血静止和抗血栓作用.
- 为了比较APAP的口服和亲肠道治疗的疗效.
主要方法:
- 在的动脉静脉 (AV) 突变中使用了一种两组分的血栓生成装置,以诱导动脉类型和静脉类型的血栓.
- 测量了血小板沉积,纤维素积累,流水阻塞和血栓形成的生化标志物.
- 通过口服和直接输液给药APAP,评估血水平和药理动力学概况.
- 评估了对结血栓结合的FXa的FXa抑制.
主要成果:
- 直接输注APAP减少了静脉类型血栓的形成 (血小板和纤维素),但没有动脉类型的血栓.
- 口服APAP (50 mg/kg) 显示生物利用率为5-12%,并减少了静脉类型血栓,但没有降低了动脉类型血栓.
- 这两种施用途径都延长了激活的部分血栓形成时间,并防止了血栓形成标志物的升高.
- APAP以剂量依赖的方式抑制了FXa与血栓结合.
结论:
- 口服的FXa抑制剂APAP有效地抑制了静脉型纤维素丰富的血栓形成.
- 通过非活化可溶性和结合性FXa.这一点,APAP实现了这一目标.
- 药物不会损害血小板血静功能,这表明它对凝血级联产生特定影响.
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