Acylated derivatives of streptokinase-plasminogen activator complex as thrombolytic agents in a dog model of aged venous thrombosis.

Abstract

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.

• Authors: R J Dupe, J Green, R A Smith
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 53 Issue 1 Pg. 56-9 (Feb 18 1985) ISSN: 0340-6245 [Print] Germany
• PMID: 3887635 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Fibrinolytic Agents
• Anistreplase
• Plasminogen
• BRL 33575
• Streptokinase

Topics

• Animals
• Anistreplase
• Disease Models, Animal
• Dogs
• Fibrinolytic Agents (therapeutic use)
• Jugular Veins
• Metabolic Clearance Rate
• Plasminogen (metabolism, therapeutic use)
• Streptokinase (metabolism, therapeutic use)
• Thrombophlebitis (blood, drug therapy, etiology)
• Time Factors