Summary
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 and the maximal percent clot lysis (c), the maximal rate of lysis (z = ¼ac · e
b
) 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).
The plasma clearance following bolus injection of staphylokinase or streptokinase
in hamsters or rabbits was comparably rapid (1.1 to 1.4 ml/min in hamsters and 14
to 15 ml/min in rabbits) as a result of a short initial half-life (1.8 to 1.9 min
in hamsters and 1.7 to 2.0 min in rabbits). These results in two quantitative rodent
models of thrombolysis suggest that staphylokinase is a potent thrombolytic agent
with an in vivo thrombolytic potency that is comparable to that of streptokinase.
Further investigation of the thrombolytic potential of staphylokinase seems to be
warranted.
