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Comparative studies of an orally-active factor Xa inhibitor, YM-60828, with other antithrombotic agents in a rat model of arterial thrombosis.

Abstract
We examined the antithrombotic activity of a novel synthetic inhibitor of factor Xa, YM-60828, in an electrically-induced carotid artery thrombosis model in rats. In the first experiment, the antithrombotic activity of YM-60828 after i.v. infusion was compared with those of heparin, darteparin and argatroban. Test drug was administered by i.v. infusion from 30 min before electrical stimulation to the end of the experiment. YM-60828 at 1 mg/kg/h significantly improved patency status, prolonged the time to occlusive thrombus formation and duration of patency. Heparin at 300 U/kg/h also improved these parameters, but were accompanied by a marked increase in systemic coagulation time. In the second experiment, the antithrombotic activity of YM-60828 after oral administration was compared with those of ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate and warfarin. Test drug was orally administered to fasted rats 60 min before electrical stimulation. YM-60828 at 30 mg/kg p.o., but not ticlopidine, cilostazol, aspirin, beraprost, ethyl icosapentate or warfarin, significantly reduced the incidence of occlusion and improved carotid arterial patency. These results suggest that YM-60828 may be a promising antithrombotic agent for the treatment and prevention of arterial thrombosis which can be given by oral as well as intravenous administration.
AuthorsT Kawasaki, K Sato, Y Sakai, F Hirayama, H Koshio, Y Taniuchi, Y Matsumoto
JournalThrombosis and haemostasis (Thromb Haemost) Vol. 79 Issue 2 Pg. 410-6 (Feb 1998) ISSN: 0340-6245 [Print] Germany
PMID9493600 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Anticoagulants
  • Factor Xa Inhibitors
  • Naphthalenes
  • Pipecolic Acids
  • Piperidines
  • Sulfonamides
  • YM 60828
  • Antithrombin III
  • Heparin
  • Arginine
  • argatroban
Topics
  • Administration, Oral
  • Animals
  • Anticoagulants (administration & dosage)
  • Antithrombin III (administration & dosage)
  • Arginine (analogs & derivatives)
  • Carotid Artery Thrombosis (drug therapy)
  • Disease Models, Animal
  • Factor Xa Inhibitors
  • Heparin (administration & dosage)
  • Infusions, Intravenous
  • Naphthalenes (administration & dosage)
  • Pipecolic Acids (administration & dosage)
  • Piperidines (administration & dosage)
  • Rats
  • Sulfonamides

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