Antithrombotic effect of a humanized anti-GPIIb/IIIa monoclonal antibody, YM207, in a photochemically induced thrombosis model in monkeys.
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.
Kaku
S
S
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Kawasaki
T
T
Sakai
Y
Y
Taniuchi
Y
Y
Yano
S
S
Suzuki
K
K
Terazaki
C
C
Kawamura
K
K
Masuho
Y
Y
Satoh
N
N
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001666:Binding Sites, Antibody / Q000187:drug effects; D001777:Blood Coagulation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010777:Photochemistry; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D012453:Saimiri; D013927:Thrombosis / Q000139:chemically induced / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D000244:Adenosine Diphosphate