Thrombolytic effect of a plasminogen-plasminogen activator chimera in a photochemically induced thrombosis (PIT) model

Br J Pharmacol. 1993 Dec;110(4):1278-9. doi: 10.1111/j.1476-5381.1993.tb13954.x.

Abstract

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.

MeSH terms

  • Animals
  • Fibrinolytic Agents / therapeutic use*
  • Male
  • Rats
  • Rats, Wistar
  • Thrombosis / drug therapy*
  • Tissue Plasminogen Activator / therapeutic use*

Substances

  • Fibrinolytic Agents
  • lanoteplase
  • Tissue Plasminogen Activator