FEASIBILITY STUDY OF A LIQUID FORMULATION OF RECOMBINANT STAPHYLOKINASE FOR CORONARY-ARTERY THROMBOLYSIS

Recombinant staphylokinase (Sak) is a highly fibrin-selective thrombol ytic agent but the optimal dose and mode of administration remain to b e defined. In view of its remarkable temperature stability (> 1.5 year s at 4 degrees C), the feasibility of using a liquid formulation of re combinant staphylokinase (Sak42D variant), which had been stored for 7 months at 4 degrees C, was tested in 10 patients with evolving acute myocardial infarction, Intravenous (i.v.) infusion over 30 min of 30 m g Sak42D induced complete coronary patency (TIMI perfusion grade 3) wi thin 90 min in eight patients, partial patency (TIMI grade 2) in one p atient and persistent occlusion in one patient, who underwent angiopla sty, At 24 h TIMI grade 3 flow was observed in all patients. No major treatment-related complication occurred. Fibrinogen levels at 90 min w ere not significantly different from baseline whereas alpha(2)-antipla smin levels were 90% of baseline. Median antibody-related Sak42D-neutr alizing activity in plasma was low at baseline (0.0 mu g/mL) and after 1 week (0.0 mu g/mL), but increased between day 7 and 10 to 12 mu g/m L, Median Anti-Sak42D IgG concentration in plasma was 7.9 mu g/mL at b aseline, 28 mu g/mL at 1 week and 190 mu g/mL at 7 to 10 days. Thus, t he liquid formulation of Sak42D induces efficient coronary artery reca nalization while preserving circulating fibrinogen and is in this resp ect indistinguishable from preparations of recombinant staphylokinase kept frozen until use. This ready to use liquid formulation of Sak42D appears to be suitable for formal phase II dose finding studies and ph ase III comparative trials.