Comparison of the antithrombotic effects of FK633, GPIIb/IIIa antagonist, and aspirin in a guinea pig thrombosis model

被引:12
作者
Aoki, T [1 ]
Cox, D [1 ]
Senzaki, K [1 ]
Seki, J [1 ]
Tanaka, A [1 ]
Takasugi, H [1 ]
Motoyama, Y [1 ]
机构
[1] Fujisawa Pharmaceut Co Ltd, New Drug Res Labs, Dept Pharmacol, Yodogawa Ku, Osaka 532, Japan
关键词
FK633; GPIIb/IIIa antagonist; aspirin; platelet; thrombosis; thrombolysis;
D O I
10.1016/S0049-3848(97)00308-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Antiplatelet and antithrombotic effects of FK633 (a GPIIb/IIIa antagonist) and aspirin were compared. FK633 at 0.32 mg/kg i,v, or aspirin at 10 mg/kg i.v. inhibited ex vivo collagen-induced aggregation by >50% for 1 hour in guinea pigs. However, aspirin was very weak in inhibiting ADP-induced aggregation. In vivo antithrombotic effects of FK633 and aspirin were compared using a FeCl3-induced carotid artery thrombosis model in guinea pigs. Pretreatment with 0.32 mg/kg i.v. of FK633 significantly prevented occlusive thrombus formation, but aspirin at 10 mg/kg i.v, did not. In thrombolysis experiments, adjunctive use of FK633 (0.32 mg/kg i.v.) with rt-PA (0.3 mg/kg bolus+1.0 mg/kg/hr) achieved reperfusion in five of five animals without reocclusion. Aspirin (10 mg/kg i.v.) with rt-PA also achieved reperfusion in three of five animals with high incidence of reocclusion. These results suggest that FK633 may be a more effective antithrombotic agent than aspirin due to its agonist-independent antiplatelet effects. (C) 1998 Elsevier Science Ltd.
引用
收藏
页码:129 / 136
页数:8
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