Comparative fibrinolytic properties of staphylokinase and streptokinase in animal models of venous thrombosis.
The thrombolytic and pharmacokinetic properties of staphylokinase were compared with those of streptokinase in hamsters with a pulmonary embolus produced from human plasma or from hamster plasma, and in rabbits with a jugular vein blood clot produced from rabbit blood. In both models, a continuous intravenous infusion of staphylokinase and streptokinase over 60 min in hamsters or over 4 h in rabbits, induced dose-dependent progressive clot lysis in the absence of significant systemic activation of the fibrinolytic system. The results of thrombolytic potency (clot lysis at 30 min after the end of the infusion, in percent, versus dose administered, in mg/kg) were fitted with an exponentially transformed sigmoidal function (formula: see text) and the maximal percent clot lysis (c), the maximal rate of lysis (z = 1/4 ac.eb) and the dose at which the maximal rate of lysis is achieved (b) were determined. In hamsters with a pulmonary embolus produced from human plasma, streptokinase had a somewhat higher thrombolytic potency than staphylokinase, as revealed by a higher z value (2,100 +/- 1,100% lysis per mg/kg streptokinase administered versus 1,100 +/- 330% lysis per mg/kg for staphylokinase). In hamsters with a pulmonary embolus produced from hamster plasma, staphylokinase had a somewhat higher thrombolytic potency than streptokinase (z = 1,600 +/- 440 versus 1,200 +/- 370% lysis per mg/kg). Staphylokinase had a higher thrombolytic potency than streptokinase in rabbits,as revealed by a higher z-value (950 +/- 350% lysis per mg/kg staphylokinase administered versus 330 +/- 39% lysis per mg/kg for streptokinase) and a lower b-value (0.035 +/- 0.010 mg/kg staphylokinase versus 0.091 +/- 0.008 mg/kg for streptokinase.(ABSTRACT TRUNCATED AT 250 WORDS)
Lijnen
H R
HR
Center for Thrombosis and Vascular Research, University of Leuven, Belgium.
Stassen
J M
JM
Vanlinthout
I
I
Fukao
H
H
Okada
K
K
Matsuo
O
O
Collen
D
D
D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007601:Jugular Veins; D008666:Metalloendopeptidases / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000378:metabolism; D011817:Rabbits; D013300:Streptokinase / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism
D005343:Fibrinolytic Agents; D013300:Streptokinase; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus