Distribution model for the intact urokinase and urokinases modified by soluble macromolecules in rat and mouse bodies

The activity of intact urokinase (UK) and urokinases modified by soluble macromolecules (dextran and dextran sulfate sodium) in a mouse body was traced after injection of the 125I-labelled enzymes. The residual fraction of the enzyme in blood can be correlated with the time (t) as follows; Xb = Ae-at + Be-bt + Ce-ct Since a greater than b greater than c, the residual fraction of the enzyme in blood chiefly depends on the magnitude of parameter C. The constant C for modified urokinase was larger than that for urokinase, showing the relative residual in blood was increased by modification of the enzyme. The apparent utilization in 50 min was 13.8% for intact UK, 28.1% for the dextran-UK and 25.2% for the sulfate dextran-UK. Therefore, the apparent utilization of UK in blood was approximately doubled by the modification. Since the half-lives of UK and modified UK in kidney and liver were not long, there were no unacceptable accumulation of the enzymes.