Fibrinogen‐immobilized Urokinase Demonstrates Increased Thrombolytic Activity in Animal Experiments

Thrombolysis strategy: Joint action of plasminogen activators. Thrombolytic compositions (A review)

“…Taking into account the high catalytic efficiency of UK (one to two orders of magnitude higher compared to the efficiency of TPA or prourokinase [3]) and the fact that conjugation with Fbg does not significantly change the catalytic properties of UK, we may expect an increase in the rate of thrombolysis by the UK-Fbg complex. Indeed, the results of comparative investigation of the properties of UK and the UK-Fbg conjugate show the possibility of decreasing the therapeutic dose and increasing the safety of thrombolysis in the latter case [11].…”

“…Previously we have conjugated UK with fibrinogen (Fbg) [ 10]. The resulting urokinase -fibrinogen (UK-Fbg) conjugate exhibited a considerable thrombolytic effect in vivo (more pronounced as compared to the native enzyme), produced a moderate influence on the systemic activation of fibrinolysis, and was characterized by a prolonged lifetime in the blood flow [11]. Increased thrombolytic activity of the conjugated UK as compared to the native enzyme (provided both taken at equal doses) is related to some special features of the protein carrier and enzymatic activity of the covalent conjugate.…”

“…A combination of these effects probably can be achieved by using a combination of plasminogen activators with different pharmacokinetics profiles and mutually complementary action. The thrombolysis triggering agent TPA is a rapidly acting short-living component [1 -3], while the UK-Fbg conjugate is a slowly acting long-living thrombolytic agent [10,11]. The joint action of this combination administered by a sequential double bolus scheme provides a rapid and stable thrombolysis in vivo [29].…”

New Strategy of Thrombolysis: Conjunctive Effect of Plasminogen Activators with Different Pharmacokinetic Profilea

“…10 This conjugation resulted in a marked thrombolytic effect in vivo produced by urokinase‐fibrinogen (uPA‐Fbg) derivatives (as compared with the action of native enzyme), revealed a moderate effect of this conjugate on the systemic activation of fibrinolysis, and prolonged uPA‐Fbg half‐life in the bloodstream. 11 Results of a comparative study of uPA and uPA‐Fbg properties suggested that this modification will decrease therapeutic doses of uPA‐Fbg and increase thrombolysis safety. 11…”

Potentiation and acceleration effects in combined administration of tissue plasminogen activator and fibrinogen-modified urokinase in dogs with modeled venous thrombosis

“…Previously we conjugated urokinase with fibrinogen [14] and such a modified urokinase preparation was found to possess pronounced and prolonged thrombolytic activity in vivo [13]. However, the development of new preparations is not the only way of enhancing the effecticiency of thrombolysis [4].…”