ANTITHROMBOTIC EFFECT OF YM-75466 IS SEPARATED FROM ITS EFFECT ON BLEEDING-TIME AND COAGULATION TIME

The antithrombotic effects of YM-75466 ([ cetimidoyl-4-piperidyl)oxy]p henyl]-N-[7-amidino-2- naphthyl)methyl]sulfamoyl]acetic acid monometha ne sulfonate!, a novel orally-active factor Xa inhibitor, and its effe cts on bleeding time and coagulation time were studied in rats and com pared with those of warfarin. Both agents were orally administered. In the venous thrombosis model, YM-75466 and warfarin inhibited thrombus formation dose-dependently, with ID50 values of 3.3 and 0.56 mg/kg, r espectively. Ex vivo study showed that both YM-75466 and warfarin prol onged prothrombin time dose-dependently, with doses, causing a two-fol d prolongation of prothrombin time in the control group, of 89 and 0.3 8 mg/kg, respectively. In bleeding time studies, YM-75466 and warfarin prolonged bleeding time dose-dependently, with doses, causing a two-f old prolongation of bleeding time in the control group, of > 100 and 0 .43 mg/kg, respectively. These results show that the antithrombotic ef fects of YM-75466 an markedly separate from its effects on bleeding ti me and coagulation time compared with warfarin. (C) 1998 Elsevier Scie nce B.V. All rights reserved.