EFFECTS OF INOGATRAN, A NEW LOW-MOLECULAR-WEIGHT THROMBIN INHIBITOR, IN RAT MODELS OF VENOUS AND ARTERIAL THROMBOSIS, THROMBOLYSIS AND BLEEDING-TIME

Inogatran (MW 439 Dal, a new, selective, active site inhibitor of thro mbin, was evaluated in three rat models of thrombosis. In the venous t hrombosis model, inogatran dose-dependently inhibited thrombus formati on with a > 80% antithrombotic effect at a plasma concentration of 0.4 5 mu mol l(-1). In the arterial thrombosis model, inogatran dose-depen dently inhibited thrombus formation, preserved vessel patency and the mean blood flow. Acetylsalicylic acid (ASA) potentiated the effects of low plasma concentrations of inogatran in the arterial thrombosis mod el. In the model of rt-PA-induced thrombolysis of a thrombus in the ca rotid artery, inogatran improved the patency time and the cumulative b lood flow during the two hour thrombolysis period more than rt-PA alon e. At high therapeutic plasma concentration of inogatran, there was on ly a moderate prolongation of bleeding time compared with the control value. It is concluded that inogatran is an effective antithrombotic a gent both in the venous and arterial thrombosis models and also as adj uvant to rt-PA in the thrombolysis model.