Antithrombotic effect of a humanized anti-GPIIb/IIIa monoclonal antibody, YM207, in a photochemically induced thrombosis model in monkeys

• Published in: European journal of pharmacology 1995-06, Vol.279 (2), p.115-121
• Main Authors: Kaku, Seiji, Kawasaki, Tomihisa, Sakai, Yumiko, Taniuchi, Yuta, Yano, Shinya, Suzuki, Ken-ichi, Terazaki, Chinami, Kawamura, Koji, Masuho, Yasuhiko, Satoh, Noboru, Takenaka, Toichi, Yanagi, Kennichi, Ohshima, Norio
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate - pharmacology; Animals; Antibodies, Monoclonal - pharmacology; Binding Sites, Antibody - drug effects; Biological and medical sciences; Bleeding time; Blood Coagulation - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Enzyme-Linked Immunosorbent Assay; Fibrinolytic Agents - pharmacology; GPIIb/IIIa; Humanized antibody; Humans; In Vitro Techniques; Medical sciences; Microcirculation; Pharmacology. Drug treatments; photochemically induced; Photochemistry; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; Platelet Glycoprotein GPIIb-IIIa Complex - immunology; Saimiri; Squirrel monkey; Thrombosis; Thrombosis - chemically induced; Thrombosis - prevention & control
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/0014-2999(95)00136-9

We investigated the antithrombotic effects of a F(ab') 2 fragment of a humanized anti-platelet glycoprotein (GP) IIb/IIIa monoclonal antibody, YM207, in a platelet-rich thrombosis model. Thrombus was induced in a mesenteric venule of squirrel monkeys by irradiation with filtered light in combination with i.v. administration of a fluorescent dye (sodium fluorescein). Time to occlusive thrombus formation was significantly prolonged by i.v. bolus injection of 0.3 mg/kg of YM207. At doses of 1 mg/kg and 3 mg/kg, complete occlusion did not occur during 60 min of the observation. Platelet aggregation in platelet-rich plasma was inhibited by YM207 at doses 0.3 mg/kg or more. A good correlation was obtained between inhibition of platelet aggregation and the percentage of GPIIb/IIIa receptors blocked by YM207. Bleeding time was significantly prolonged at a dose of 3 mg/kg. Platelet counts showed no significant change. These results suggest that YM207 is effective in preventing platelet-rich thrombus formation without inducing the prolongation of bleeding time or a significant decrease in platelet count. YM207 may be a useful therapeutic agent for the treatment of thrombotic disorders.