Thrombolytic effect of a plasminogen-plasminogen activator chimera in a photochemically induced thrombosis (PIT) model.
The thrombolytic effects of the plasminogen/plasminogen activator chimera (SUN9216), comprising the fibrin-binding kringle 1 domain of plasminogen and two kringle and the serine protease domain of the wild-type tissue plasminogen activator (t-PA) including a modification of the mannose glycosylation on the kringle 1 of t-PA (PK1 delta FE1X), was compared with tht of t-PA by use of a photochemically induced thrombus (PIT) in the rat femoral artery. When SUN9216 was administered either as an i.v. infusion (1.0 mg kg-1) or as a single bolus i.v. injection (1.0 mg kg-1), all parameters were markedly improved compared to t-PA administered as an i.v. infusion (3.0 mg kg-1). A higher concentration of plasminogen activator (PA) activity in plasma was observed after administration of SUN9216 which persisted for longer than that after t-PA. It is concluded that the thrombolytic effect of SUN9216 is markedly greater than that of t-PA.
Matsuno
H
H
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Uematsu
T
T
Nakashima
M
M
D000818:Animals; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; C081981:lanoteplase; D010959:Tissue Plasminogen Activator