Comparison of the Anticoagulant and Antithrombotic Effects of YM-75466, a Novel Orally-Active Factor Xa Inhibitor,and Warfarin in Mice

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Author(s)

Abstract

The anticoagulant and antithrombotic effects of YM-75466 (<I>N</I>-[4-[(1-acetimidoyl-4-piperidyl) oxy]phenyl]-<I>N</I>-[(7-amidino-2-naphthyl)methyl]sulfamoyl acetic acid monomethanesulfonate), a novel orallyactive factor Xa (FXa) inhibitor, and warfarin were compared in mice. Both agents were orally administered in all studies. In ex vivo studies, the peak effects of YM-75466 occurred 1 hr after administration while the peak of warfarin activity occurred 18 hr after administration. At each peak, both YM-75466 and warfarin prolonged coagulation time dose-dependently. The dose response curve of warfarin for prothrombin time was steeper than that of YM-75466. In a thromboplastin-induced thromboembolism model, administration of 30 mg/kg YM-75466 or 3 mg/kg warfarin significantly improved the lethality ratio. In blood loss studies, YM-75466 did not increase blood loss from the tail even at 30 mg/kg, while warfarin markedly increased blood loss at 3 mg/kg. Agents that interfere with warfarin action did not interfere with YM-75466 action. In conclusion, this study shows that YM-75466 has advantages over warfarin: i) rapid onset of anticoagulant activity, ii) wide therapeutic range, iii) little effect on bleeding and iv) lack of drug interaction with agents that interfere with warfarin. These results suggest that YM-75466 may be promising as a novel oral anticoagulant agent.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 78(2), 191-197, 1998-10-01

    The Japanese Pharmacological Society

References:  19

Codes

  • NII Article ID (NAID)
    10008680764
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4591516
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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