In vitro and in vivo studies of the novel antithrombotic agent BAY 59‐7939—an oral, direct Factor Xa inhibitor

摘要: BAY 59-7939 is an oral, direct Factor Xa (FXa) inhibitor in development for the prevention and treatment of arterial venous thrombosis. competitively inhibits human FXa (K(i) 0.4 nm) with > 10 000-fold greater selectivity than other serine proteases; it also inhibited prothrombinase activity (IC(50) 2.1 nm). endogenous more potently rabbit plasma 21 rat 290 It demonstrated anticoagulant effects plasma, doubling prothrombin time (PT) activated partial thromboplastin at 0.23 0.69 microm, respectively. In vivo, reduced thrombosis (fibrin-rich, platelet-poor thrombi) dose dependently (ED(50) 0.1 mg kg(-1) i.v.) a stasis model. (fibrin- platelet-rich) thrombus formation arteriovenous (AV) shunt rats 5.0 p.o.) rabbits 0.6 p.o.). Slight inhibition (32% ED(50)) model; to affect rabbit, stronger (74%, 92% was required. Calculated levels ED(50) were 14-fold lower AV model, correlating IC(50) compared plasma; this may suggest correlation between antithrombotic activity. Bleeding times not significantly affected doses (3 p.o., shunt). Based on these results, selected clinical development.