Development of eptifibatide
Development of eptifibatide
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DOI：
10.1016/s0002-8703(99)70075-x
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发表时间：
1999-12-01
影响因子：
4.8
通讯作者：
Scarborough, RM
中科院分区：
文献类型：
--
作者：
Scarborough, RM
背景 急性冠状动脉综合征的主要原因是血栓的形成，血栓是血小板聚集的病理表现，是正常止血过程的一部分。血小板聚集的最后一个共同步骤是通过纤维蛋白原与活化的血小板整合素糖蛋白 (GP) IIb/IIIa 结合，这一发现为开发新型且可能更有效的抗血栓疗法打开了大门。 Abciximab 是针对 GP IIb/IIIa 受体的单克隆抗体的人鼠嵌合 Fab 片段，是此类药物中第一个证明临床有效性的药物。阿昔单抗的一些特殊特性，例如其半衰期长、缺乏受体阻断特异性以及一些抗原性倾向，促使人们开发出具有独特药理学特征的替代 GP IIb/IIIa 抑制剂。 方法和结果 其中一种较新的药物是依替巴肽，它是通过模仿在东南侏儒响尾蛇的毒液中发现的 GP IIb/IIIa 阻断剂 barbourin 开发的。依替巴肽是一种小型环状七肽，对 GP IIb-IIIa 具有高特异性和高亲和力，血浆半衰期短，抗血小板作用起效快，治疗停止后血小板抑制可快速可逆。 结论 在临床试验中，III 期 IMPACT II（Integrilin 最大限度减少血小板聚集和冠状动脉血栓形成）和 PURSUIT（血小板 GP）达到顶峰。 IIb-IIIa（使用整合素疗法抑制不稳定型心绞痛）试验中发现，依替巴肽可显着减少广泛的低、中、高危急性冠状动脉综合征患者的冠状动脉事件，而不会显着增加出血或其他并发症的风险。这些结果表明依替巴肽可能被证明是当前可用的抗血栓治疗的有效补充。
Background The primary cause of acute coronary syndromes is the development of a thrombus, a pathologic manifestation of platelet aggregation that occurs as part of the normal process of hemostasis. The discovery that the final common step in platelet aggregation, through the binding of fibrinogen to the activated platelet integrin glycoprotein (GP) IIb/IIIa, has opened the door to the development of novel and potentially more effective antithrombotic therapies. Abciximab, a human-murine chimeric Fab fragment of a monoclonal antibody against the GP IIb/IIIa receptor, was the first agent of this class to demonstrate clinical effectiveness. Several of the specific properties of abciximab, such as its long half-life, lack of receptor-blocking specificity, and some tendency for antigenicity, have prompted the development of alternative GP IIb/IIIa inhibitors with distinct pharmacologic profiles.Methods and Results One of these newer agents is eptifibatide, which was developed by mimicking the GP IIb/IIIa blocker barbourin, found in the venom of the southeastern pigmy rattlesnake. Eptifibatide is a small, cyclic heptapeptide that has shown high specificity and high affinity for GP IIb-IIIa, a short plasma half-life, and rapid onset of antiplatelet action accompanied by a rapid reversibility of platelet inhibition once treatment is stopped.Conclusions In clinical trials, culminating in the phase III IMPACT II (Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis) and PURSUIT (Platelet GP IIb-IIIa in Unstable Angina. Receptor Suppression Using Integrilin Therapy) trials, eptifibatide was found to reduce coronary events significantly in a broad range of low-, medium-, and high-risk patients with acute coronary syndromes without significantly increasing the risk of bleeding or other complications. These results suggest that eptifibatide may prove to be an effective addition to currently available antithrombotic therapies.