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

Abstract

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.

• Authors: T Aoki, D Cox, K Senzaki, J Seki, A Tanaka, H Takasugi, Y Motoyama
• Journal: Thrombosis research (Thromb Res) Vol. 89 Issue 3 Pg. 129-36 (Feb 01 1998) ISSN: 0049-3848 [Print] United States
• PMID: 9622041 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Dipeptides
• Fibrinolytic Agents
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• Recombinant Proteins
• ((4-(4-amidinophenoxy)butanoyl)aspartyl)valine
• Tissue Plasminogen Activator
• Aspirin

Topics

• Animals
• Aspirin (administration & dosage)
• Carotid Artery Thrombosis (blood, drug therapy)
• Dipeptides (administration & dosage)
• Fibrinolytic Agents (administration & dosage)
• Guinea Pigs
• Injections, Intravenous
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Recombinant Proteins (administration & dosage)
• Tissue Plasminogen Activator (administration & dosage)