[Pharmacological studies of intracoronary administered urokinase]

The pharmacokinetics of intracoronary administered urokinase was investigated in anesthetized open-chest dogs, together with its effect on the cardiovascular system, and the influence of urokinase in isolated guinea-pig heart was also examined. After intracoronary administration of 20,000 IU/kg of 125I-urokinase, radioactivity in plasma was eliminated biexpomentially with half-lives of 6.8 min and 4.4 hr. At 4 hr after the administration of 125I-urokinase, 32% of the total radioactivity remained in the TCA-insoluble fraction of plasma, and only 0.13% of the administered radioactivity was excreted as a TCA-insoluble fraction in the urine, suggesting that the administered urokinase may be metabolized for the most part into low molecular weight compounds. In hemodynamic measurements, we observed some decrease in cardiac function which was thought to be attributable to bleeding from the incision of open-chest surgery, probably caused by the fibrinolytic activity of urokinase, and urokinase, up to the dose of 2,000,000 IU/kg (approximately 100 times of therapeutic dose), did not appear to show any direct action on the cardiovascular system. This result was supported by the fact that urokinase (10,000-1,000,000 IU/heart) did not have any effects on contractile force, heart rate and coronary flow in isolated guinea-pig heart. From these results, we confirmed that the pharmacokinetics of intracoronary administered urokinase was essentially the same as that of intravenously administered urokinase and that intracoronary administered urokinase showed virtually no direct effect on the cardiovascular system.