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Tirofiban versus abciximab: tirofiban is administered at suboptimal dosages when evaluated in an arterial thrombosis model in non-human primates.

机译:替罗非班与阿昔单抗:在非人灵长类动物的血栓形成模型中评估时,替罗非班以次优剂量给药。

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摘要

To prevent thrombosis in high-risk acute coronary syndrome patients undergoing percutaneous coronary intervention for re-vascularisation, concomitant administration of a glycoprotein IIb/IIIa inhibitor, such as abciximab, tirofiban or eptifibatide, is recommended. Abciximab and eptifibatide are mostly preferred over tirofiban, which is less effective in preventing ischaemic events. We compared the efficacy and bleeding potential of escalating doses of tirofiban and abciximab in non-human primates. The efficacy of tirofiban and abciximab in inhibiting cyclic flow reductions (CFRs) was tested in a high shear arterial thrombosis model. Bleeding was evaluated with the template bleeding time and an incision bleeding model. Abciximab completely inhibited arterial thrombosis after injection of its therapeutic bolus dose. With tirofiban, a dose three times higher than the recommended therapeutic dose caused weak inhibition characterised by a return of CFRs after re-injury. At nine times the recommended therapeutic dose, complete inhibition was observed, and the efficacy of tirofiban was comparable to abciximab at its therapeutic bolus dose. Blood loss was less than with abciximab at its effective dose. In this model, tirofiban compared favourably with abciximab, although only at a dose of 3-9 times the therapeutic dose, and caused less bleeding than abciximab.
机译:为防止高危急性冠状动脉综合征患者在接受经皮冠状动脉介入治疗以进行血管重建时血栓形成,建议同时给予糖蛋白IIb / IIIa抑制剂,例如abciximab,替罗非班或依替非巴肽。阿昔单抗和依替巴肽比替罗非班更受青睐,后者在预防缺血性事件中作用较差。我们比较了递增剂量的替罗非班和阿昔单抗在非人类灵长类动物中的疗效和出血潜力。在高剪切动脉血栓形成模型中测试了替罗非班和阿昔单抗抑制循环血流减少(CFR)的功效。用模板出血时间和切口出血模型评估出血情况。注射治疗剂量后,阿昔单抗完全抑制了动脉血栓形成。使用替罗非班时,比推荐治疗剂量高三倍的剂量会导致抑制作用较弱,其特征是再次受伤后CFR恢复。在推荐治疗剂量的九倍时,观察到完全抑制,并且在其推注剂量下,替罗非班的疗效与阿昔单抗相当。在有效剂量下,失血量少于阿昔单抗。在该模型中,替罗非班与阿昔单抗相比具有优势,尽管其剂量仅为治疗剂量的3-9倍,并且出血量少于阿昔单抗。

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