Saruplase: in combination with alteplase for thrombolysis in patients with MI

R&D

As a result of nonspecific plasminogen activation, the beneficial effects of streptokinase and urokinase are negated by the adverse haemostatic effects of plasminaemia. Alteplase and saruplase [pro-urokinase, single chain urokinase plasminogen activator, scu-PA, PUK. CG 4509, Thrombolyse; Genentech] are known to have relatively specific fibrinolytic actions, however, the dosage required to achieve clinical thrombolysis causes nonspecific plasminogen activation. Because these agents act synergistically, a study was conducted to determine whether the combination of alteplase and saruplase would result in significant specific thrombolysis. Under heparin control, 38 patients with acute myocardial infarction (MI; presenting within 6 hours after pain onset) received a bolus of saruplase 3.7mg, followed by a simultaneous infusion of saruplase 44.3mg over 40 min and alteplase 12mg over 30 min.

At 60 and 90 min, respectively, angiography revealed patency of the infarct vessel in 61.3 and 81.8% of evaluable patients. Fibrinogen levels decreased to 82.8 and 91.2% of baseline levels at 60 and 120 min, respectively, mean plasminogen concentration levels decreased to 66.3 and 65.3% of baseline, and alpha2 anti plasmin levels decreased to 30.7 and 32.2% of baseline.

Combination therapy was well tolerated; mean haemoglobin levels were 87.9% of baseline levels at day I and no bleeding episodes occurred. A significant degree of stenosis was present in all patients after thrombolytic therapy.

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Bode C, Schuler G, Nordt T. ScbOnermark S, Baumann H, et aI. Intravenous thrombolytic therapy with a combination of single~hain urokinase-type plasminogen activator and recombinant tissue-type plasminOlCD activator in acute myocardial infarction. Circulation 81: 907-913, Mar 1990 1244

ISSN 0J56-1703/90/0630-0003/0r,OJ.00/0 <!) Adis l"tertllltio"IIJ Ltd

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