Comparison of the Antithrombotic Effects of FK633, GPIIb/IIIa Antagonist, and Aspirin in a Guinea Pig Thrombosis Model

• Published in: Thrombosis research Vol. 89; no. 3; pp. 129 - 136
• Main Authors: Aoki, Toshiaki, Cox, Dermot, Senzaki, Kayoko, Seki, Jiro, Tanaka, Akito, Takasugi, Hisashi, Motoyama, Yukio
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 01-02-1998; Elsevier Science
• Subjects: Animals; Aspirin; Aspirin - administration & dosage; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Carotid Artery Thrombosis - blood; Carotid Artery Thrombosis - drug therapy; Dipeptides - administration & dosage; Fibrinolytic Agents - administration & dosage; FK633; GPIIb/IIIa antagonist; Guinea Pigs; Injections, Intravenous; Medical sciences; Pharmacology. Drug treatments; Platelet; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - administration & dosage; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors; Recombinant Proteins - administration & dosage; Thrombolysis; Thrombosis; Tissue Plasminogen Activator - administration & dosage; Aspirin; Platelet; GPIIb/IIIa antagonist; RGD, Arg-Gly-Asp; GPIIb/IIIa, glycoprotein IIb/IIIa; FK633; rt-PA, recombinant tissue plasminogen activator; Thrombosis; Thrombolysis; Glycoprotein IIbIIIa; Intravenous administration; Rodentia; Cardiovascular disease; Acetylsalicylic acid; Antiplatelet agent; Vascular disease; Vertebrata; Chemotherapy; Mammalia; Guinea pig; Treatment; Animal; Antagonist; Salicylates; Comparative study; Biological receptor
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/S0049-3848(97)00308-3

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 FeCl
3-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.