FK633: A Potent and Selective Platelet GPIIb/IIIa Antagonist

Platelet activation and aggregation have been shown to play a central role in thromboembolic disorders (20,35,37). Platelets are activated by a variety of agonists. They adhere to the injured blood vessel walls and, subsequently, aggregate. These processes lead to the formation of occlusive thrombi in the lumen of the injured vessel (16,23,53). The efficacy of such common antiplatelet agents as aspirin and ticlopidine is limited because they inhibit only some of the many pathways in platelet activation (2,33,39). Antagonism of the platelet glycoprotein (GP) IIb/IIIa receptor represents an attractive antiplatelet strategy, because it inhibits the final common step in platelet aggregation irrespective of the inducing agonist (3,12,13). The inhibition of platelet function with some GPIIb/IIIa antagonists has led to significant clinical benefits in reducing acute coronary ischemic syndrome (47–49). FK633 is a potent and selective GPIIb/IIIa antagonist that inhibits human platelet aggregation induced by a wide variety of agonists (3). In vivo experiments suggest that it is effective in the prevention of arterial thrombus formation and in the suppression of reocclusion and restenosis in the injured vessel after thrombolysis (3,4,28). In this review, we present the pharmacological profile, pharmacokinetics, toxicology, and some clinical data on FK633, and discuss the future direction for GPIIb/IIIa antagonists.