Orally bioavailable anticoagulants are needed that exhibit rapid and predictable onset and offset kinetics. This study was designed to determine whether maltodapoh, a novel sulfated bis-maltobionic acid amide, exhibits anticoagulant and antithrombotic activity in vivo after oral administration. Maltodapoh exhibited a dose-dependent increase in activated partial thromboplastin time (aPTT) in both rabbit and human plasma in vitro. Maltodapoh also induced a dose-dependent increase in aPTT when administered either i.v. or p.o. in rabbits. After a single oral bolus (3 mg/kg), aPTT increased 2- to 3-fold between 4 and 8 h and remained elevated for at least 24 h. This dose doubled the time to the onset of thrombotic occlusion after electrical injury to the carotid artery (from 52 ± 12 min in vehicle- treated, control rabbits, n = 7, to 98 ± 12 min in maltodapoh-treated animals, n = 7, P < .001) and reduced by 84% the weight of thrombus in the superior vena cava induced over 2 h after insertion of a thrombogenic copper wire and thread device (from 37 ± 10 mg in controls to 6 ± 3 mg in maltodapoh-treated animals, P < .001). Thus, based on the in vivo activity after oral administration, favorable kinetic profile and efficacy for inhibition of both arterial and venous thrombosis, further testing of this class of compounds appears warranted.
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Feb 1999|