Effect of a humanized monoclonal antibody to von Willebrand factor in a canine model of coronary arterial thrombosis.
The purpose of this study was to investigate the antithrombotic effect and bleeding time prolongation of AJW200, a humanized monoclonal antibody to von Willebrand factor (vWF), in a canine model of coronary arterial thrombosis. AJW200 significantly inhibited cyclic flow reductions, as well as botrocetin-induced platelet aggregation, at 0.1 mg/kg. A significant prolongation of bleeding time was observed at 0.3-1 mg/kg. Approximately 50% occupancy of vWF (approximately 0.7 microg/ml AJW200 in plasma) and 80-100% occupancy (approximately 20 microg/ml AJW200 in plasma) were needed for the antithrombotic effect and the extensive prolongation of bleeding time, respectively. On the contrary, the minimal effective dose of abciximab (0.8 mg/kg) was associated with a significant prolongation of bleeding time. These results suggest that the pharmacological blockade of platelet glycoprotein (GP) Ib-vWF interaction with AJW200 results in a safer antithrombotic profile than platelet GPIIb/IIIa blockade with abciximab in dogs.
Kageyama
Shunsuke
S
Discovery Research Laboratories, Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., 1-1 Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-8681, Japan.
Matsushita
Junko
J
Yamamoto
Hiroshi
H
D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D003328:Coronary Thrombosis / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D005343:Fibrinolytic Agents / Q000097:blood / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000494:pharmacology*; D011517:Prothrombin Time; D014841:von Willebrand Factor / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D000077284:Abciximab