Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 443, Issue 1-3, Pages 143-149Publisher
ELSEVIER
DOI: 10.1016/S0014-2999(02)01590-X
Keywords
von Willebrand factor (vWF); platelet; thrombosis; bleeding time; AJW200
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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 mug/ml AJW200 in plasma) and 80-100% occupancy (approximately 20 mug/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. (C) 2002 Elsevier Science B.V. All rights reserved.
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