Acylated derivatives of streptokinase-plasminogen activator complex as thrombolytic agents in a dog model of aged venous thrombosis.
A procedure is described for the establishment of experimental clots, aged in vivo for 72 hr, in the jugular vein of beagle dogs. Two acylated derivatives of streptokinase-human (lys) plasminogen activator complex with greatly differing deacylation rates under physiological conditions were compared as thrombolytic agents in the model. These were BRL 26921 (deacylation half-life, 40 min) and BRL 33575 (deacylation half-life c. 17 hr). The pharmacokinetic clearance rate of BRL 33575 from the circulation was studied and gave a clearance half-life of about 7 hr. BRL 33575 was found to be the superior agent in lysing 72 hr aged clots, being effective at a single bolus dose of 420 micrograms/kg or in three equal divided doses of 140 micrograms/kg given at 12 hr intervals. The single dose regime gave moderate systemic plasminogen activation, and the effect was significantly reduced with the divided dose regime. Infusion of freshly formed streptokinase-human plasminogen activator complex at 420 micrograms/kg over 15 hr gave little thrombolysis despite marked systemic plasminogen activation.
D000818:Animals; D016255:Anistreplase; D004195:Disease Models, Animal; D004285:Dogs; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D007601:Jugular Veins; D008657:Metabolic Clearance Rate; D010958:Plasminogen / Q000378:metabolism / Q000627:therapeutic use*; D013300:Streptokinase / Q000378:metabolism / Q000627:therapeutic use*; D013924:Thrombophlebitis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D013997:Time Factors
D005343:Fibrinolytic Agents; D016255:Anistreplase; D010958:Plasminogen; C043149:BRL 33575; D013300:Streptokinase