Comparison of the antithrombotic effects of FK633, GPIIb/IIIa antagonist, and aspirin in a guinea pig thrombosis model.
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 (10O 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.
Aoki
T
T
Department of Pharmacology, New Drug Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan. toshaikivaoki@rnd.fujisawa.co.jp
Cox
D
D
Senzaki
K
K
Seki
J
J
Tanaka
A
A
Takasugi
H
H
Motoyama
Y
Y
D000818:Animals; D001241:Aspirin / Q000008:administration & dosage*; D002341:Carotid Artery Thrombosis / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000008:administration & dosage*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006168:Guinea Pigs; D007275:Injections, Intravenous; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000008:administration & dosage; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage
D004151:Dipeptides; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; C103087:((4-(4-amidinophenoxy)butanoyl)aspartyl)valine; D010959:Tissue Plasminogen Activator; D001241:Aspirin