Preclinical Drug Testing Facility, Department of Haematology and Cell Biology (G2), Faculty of Health Sciences, University of the Free State, PO Box 339, Bloemfontein 9300, South Africa.
Clin Exp Med. 2012 Dec;12(4):257-63. doi: 10.1007/s10238-011-0171-4. Epub 2012 Jan 5.
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.
为预防经皮冠状动脉介入治疗血运重建的高危急性冠脉综合征患者发生血栓形成，建议同时使用糖蛋白 IIb/IIIa 抑制剂，如阿昔单抗、替罗非班或依替巴肽。阿昔单抗和依替巴肽比替罗非班更常用，因为替罗非班在预防缺血事件方面效果较差。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）的效果。用模板出血时间和切口出血模型评估出血。阿昔单抗注射治疗剂量后可完全抑制动脉血栓形成。替罗非班的剂量比推荐的治疗剂量高 3 倍，仅能引起微弱抑制，表现为再损伤后 CFR 恢复。在推荐治疗剂量的 9 倍时，观察到完全抑制，替罗非班的疗效与阿昔单抗的治疗剂量相当。与阿昔单抗的有效剂量相比，出血较少。在该模型中，替罗非班与阿昔单抗相比具有优势，尽管仅在治疗剂量的 3-9 倍时如此，且出血比阿昔单抗少。
