Thrombolytic Activity of a Novel Modified Tissue-Type Plasminogen Activator, YM866, in a Canine Model of Coronary Artery Thrombosis

The Japanese Journal of Pharmacology

Chuichi Kawai¹  Tomihisa Kawasaki²  Toichi Takenaka²  Yoshiki Yui¹  Seiji Kaku²  Hiroshi Gushima²  Masao Katoh² 

[1] Third Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, Kyoto 606-01, Japan;Cardiovascular and Atherosclerosis Research Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305, Japan

关键词: Tissue-type plasminogen activator (t-PA) (modified);    Thrombosis (copper coil-induced);    Thrombi (aged);    Coronary thrombolysis;   

DOI  :  10.1254/jjp.63.9

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(31)Cited-By(15)The thrombolytic activity of a novel modified t-PA, YM866, was compared with that of a recombinant t-PA in a canine model of copper coil-induced coronary thrombosis. The coronary thrombus was allowed to age for 1, 3 or 6 hr before either drug was administered. YM866 was administered by i.v. bolus injection, while t-PA was given by the same method, as well as by 60-min i.v. infusion. YM866 showed thrombolytic activity 2 to 4 times as potent as that of t-PA when administered by bolus injection, the difference in thrombolytic effect being obvious in the 3 and 6-hr-old thrombi. Coronary reperfusion was achieved more rapidly with YM866 than with i.v. infusion of t-PA. In animals injected with doses of more than 0.1 mg/kg of YM866, no acute reocclusion occurred. Depletion of plasma fibrinogen to 70% of baseline levels was observed in animals given 0.2 mg/kg YM866, 0.4 mg/kg t-PA by bolus, and 0.6 mg/kg t-PA via infusion. The residual plasma YM866 and t-PA antigen 30 min after bolus injection was 25% and 3% of the peak levels, respectively. YM866, administered by i.v. bolus injection, was thus confirmed to exert a thrombolytic effect superior to that of bolus injection and infusion of t-PA, without systemic fibrinolytic activation. These results suggest the potential clinical applicability of YM866 as a thrombolytic agent that can be administered by i.v.bolus injection for acute myocardial infarction.

【 授权许可】

Unknown