Comparison of the Pharmacokinetics and Effects on the Hemostatic System of Saruplase and Urokinase in Patients with Acute Myocardial Infarction.

The aim of the study was to compare in a single trial, using identical methodology, the pharmacokinetic properties and the effect on the hemostatic system of saruplase (unglycosylated scu-PA) and urokinase (glycosylated tcu-PA). Twenty-four patients with an acute myocardial infarction were either treated with saruplase (n = 12; 20 mg IV bolus followed by a 60 mg infusion for 60 minutes) or urokinase (n = 12; 1.5 million IU IV bolus followed by 1.5 million IU infusion for 60 minutes). Blood samples from saruplase-treated patients were analyzed for u-PA antigen and total u-PA and tcu-PA activities; those from urokinase-treated patients for u-PA antigen and tcu-PA activity. The effect of treatment on, including recovery of, plasma alpha2-antiplasmin, fibrinogen, and plasminogen was examined in both groups. The total clearance of urokinase (179 +/- 55 ml/min) is about half that of saruplase (406 +/- 154 ml/min), and the mean residence time of urokinase (59.1 +/- 22.5 minutes) is nearly twice that of saruplase (28.3 +/- 7.8 minutes), which results in a slower elimination of urokinase from plasma. Whether differences in the pharmacokinetic behavior of the unglycosylated saruplase and the glycosylated urokinase observed in this study are due to the difference in glycosylation or to other factors is not resolved. The systemic effect of saruplase on alpha2-antiplasmin, fibrinogen, and plasminogen is similar to that of urokinase, although retarded.