Sasahara A A, Barker W M, Weaver W D, Hartmann J, Anderson J L, Reddy P S, Villiard E M
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
J Vasc Interv Radiol. 1995 Nov-Dec;6(6 Pt 2 Suppl):84S-93S. doi: 10.1016/s1051-0443(95)71255-6.
Recombinant prourokinase (r-ProUK) is a single-chain urokinase-type plasminogen activator that is produced from a mammalian cell line. It is administered as a zymogen and remains inactive until converted to the active two-chain form on the surface of a clot. The clot specificity of this agent, therefore, is conferred by the site of conversion to the active form on the surface of the clot. Two pilot studies were conducted to evaluate the safety and efficacy of r-ProUK in patients with acute myocardial infarction. In the first study, the 90-minute patency rate was 66.7% in 21 patients receiving 60 mg over 60 minutes and 72.2% in 18 patients receiving 60 mg over 90 minutes. In the second study, the 90-minute patency rates were 45.5% in the group primed with recombinant urokinase who were given 60 mg of r-ProUK infused over 60 minutes (11 patients) and 80.8% in the primed group given 60 mg infused over 90 minutes (26 patients). Only 4.6% of patients experienced severe bleeding complications, with no patient developing intracranial hemorrhage. These two studies describe the first application of r-ProUK in patients. Although two doses were selected for evaluation, the small number of patients studied did not permit the selection of one dose as superior to the other. The results, however, did indicate that r-ProUK is a very effective thrombolytic agent in achieving patency of occluded coronary arteries. It is especially effective in maintaining coronary patency, having shown only a 1.4% rate of reocclusion. Serious bleeding complications were few and no intracranial hemorrhages were noted in this group of 131 patients. Additional clinical trials will be needed to compare the efficacy of r-ProUK with that of other available thrombolytic agents.
