Protective effect of oral xemilofiban in arterial thrombosis in dogs - Increased activity in combination with aspirin

Article

关键词: PLATELET-AGGREGATION;    CANINE MODEL;    ANTITHROMBOTIC EFFICACY;    GPIIB/IIIA ANTAGONIST;    MYOCARDIAL-INFARCTION;    RECEPTOR ANTAGONIST;    BLOOD-FLOW;    INHIBITION;    BLOCKADE;    SC-54684A;   

DOI  :  10.1161/01.CIR.98.8.813

来源: SCIE

【 摘 要 】

Background-Inhibition of platelet aggregation by preventing the binding of fibrinogen to glycoprotein (GP) IIb/IIIa on activated platelets results in antithrombotic activity. We report on the antithrombotic effect of xemilofiban (SC-54684A), an oral GP IIb/IIIa antagonist, administered alone or with aspirin (ASA) in an acute thrombosis model. Methods and Results-Conscious dogs were treated with xemilofiban (1.25, 2.5, 5.0, or 6 mg/kg, n=6); low-dose (LD, 81 mg) ASA, n=7; high-dose (HD, 162 mg) ASA, n=6; xemilofibran 1.25 mg/kg plus LD ASA, n=6; xemilofibran 1.25 mg/kg plus HD ASA, n=6; or placebo, n=7. Dogs were anesthetized 60 minutes later, and the effects of the treatments were evaluated after electrolytic injury (250 mu A for 180 minutes) in the left circumflex coronary artery. Bleeding time (BT) was assessed in a separate study. Incidence of thrombosis was reduced (P<0.05) by xemilofiban greater than or equal to 2.5 mg/kg, HD ASA, or xemilofiban 1.25 mg/kg plus HD ASA compared with placebo. Xemilofiban greater than or equal to 2.5 mg/kg or xemilofiban 1.25 mg/kg plus HD ASA significantly increased time to occlusion, inhibited ex vivo platelet aggregation to collagen >90%, and prevented or decreased (P<0.05) cyclic flow variations (CFVs) compared with placebo. BT was increased (P<0.05) with xemilofiban greater than or equal to 2.5 mg/kg but not with xemilofiban 1.25 mg/kg plus HD ASA. Conclusions-Xemilofiban greater than or equal to 2.5 mg/kg, HD ASA, or xemilofiban 1.25 mg/kg plus HD ASA significantly reduced the incidence of thrombosis. These doses of xemilofiban or xemilofiban 1.25 mg/kg plus HD ASA increased time to occlusion, inhibited ex vivo platelet aggregation by >90%, and prevented or reduced CFVs. Xemilofiban greater than or equal to 2.5 mg/kg but not xemilofiban 1.25 mg/kg plus HD ASA significantly increased BT.

【 授权许可】

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