Saruplase is a clinically safe and effective thrombolytic medication. This profile ranks saruplase favorably among the currently available thrombolytic agents.
In acute myocardial infarction, the administration of a heparin bolus before thrombolytic therapy with saruplase is associated with a significantly higher patency at angiography 6 to 12 h after the start of thrombolysis without any appreciable increase in risk of bleeding.
Background: Urokinase or two-chain urokinase-type plasminogen activator has been shown to be effective in the treatment of acute myocardial infarction. Its parent molecule, single-chain urokinase-type plasminogen activator (scu-PA), unlike urokinase, can selectively activate fibrin-bound plasminogen. The induced clot lysis is amplified by plasmin-triggered conversion of scu-PA to urokinase and by further plasmin generation. The aim of our study was to compare the efficacy and safety of recombinant unglycosylated scu-PA, or saruplase, and urokinase at doses considered optimal in patients with acute myocardial infarction within 6 hours of onset of pain. Methods and results: In a double-blind trial 543 patients were randomized to saruplase (20 mg bolus + 60 mg/hr) or urokinase (1.5 million unit bolus + 1.5 million units/hr). Primary endpoint: The patency rates at 24-72 hours were 75.4% (95% CI 70.3-80.5%) for saruplase and 74.2% (95% CI 69.0-79.4%; P = 0.77) for urokinase. Secondary endpoint: The incidence of bleeding events in both groups was 10.7%. There were three hemorrhagic strokes in the saruplase group (ns). Other efficacy and safety evaluations: Apart from the generation of more fibrinogen degradation products under saruplase, the changes in hemostatic parameters did not differ. Hospital mortality was 4.4% for saruplase and 8.1% for urokinase. This nonsignificant difference was maintained for 1 year. Conclusion: The efficacy and safety of saruplase and urokinase in the regimens used are very similar.
SummaryWe examined in patients with acute myocardial infarction (AMI) the pharmacokinetics of saruplase, an unglycosylated, single chain, urokinase-type plasminogen activator (rscu-PA) by measuring urokinase-type plasminogen activator (u-PA) antigen and total u-PA activity, its conversion to active two-chain urokinase-type plasminogen activator (tcu-PA) and evaluated its effect on haemostatic parameters.Twelve patients were studied during and after administration of 20 mg bolus plus 60 mg continuous 1 h i.v. infusion of saruplase. For u-PA antigen and total u-PA activity (expressed as protein equivalents), where 234 U corresponds to 1 μg, respectively, steady state plasma concentrations were 2.75 ± 8.3 and 2.50 ± 7.0 μg/ml (mean ± standard deviation) and were reached within 20min, t1/2M was 9.1 ± 1.8 and 7.8 ± 1.3 min, t1/2λ2 1.2 ± 0.2 and 1.9 ± 0.5 h, and the total clearance was 393 ±110 and 427 ± 113 ml/min. Inactivation of saruplase in plasma was negligible.After 15 min, tcu-PA was detected in plasma. From the ratio of the areas under the curve of tcu-PA and total u-PA activities it was calculated that 28 ± 9.3% of the saruplase dose is converted into active tcu-PA. Systemic plasminaemia occurs as shown by a decrease in α2-antiplas-min and fibrinogen and an increase in fibrinogen degradation products. Thrombin-antithrombin complex formation indicated activation of the clotting system.Saruplase is eliminated rapidly from plasma in AMI patients. A variable, but significant proportion of saruplase is converted into active tcu-PA. At the end of the infusion tcu-PA accounted for 55% of total u-PA activity. Systemic plasmin generation and activation of the clotting system occur during saruplase treatment for AMI.
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