Studies on metabolism of urokinase and mechanism of thrombolysis by urokinase.
Pharmacokinetics of intravenously injected 125I-labeled urokinase (125I-UK) of a molecular weight of 33,000 daltons in normal rabbits and patients with various diseases were investigated. The plasma clearance of 125I-UK in rabbits was described by a biexponential curve within six hours with a half-life of 8 minutes, 2.3 hours, respectively. The radioactivity in the liver and kidneys 15 minutes after iv injection with 125I-UK was 9.6% and 14.0% of the radioactivity injected, respectively. Approximately 80% of the total radioactive material injected was excreted in the urine in 18 hours. No increase in activator activity in the urine was observed after a large amount of UK injection. Activity uptake of 125I-UK by experimentally induced arterial thrombus was little. Lysis of the stasis thrombus was produced by injecting 7.5 x 10(-4) IU of UK in only one out of 8 rabbits. In vitro contact experiment revealed that transfer of 125I-UK to plasma clot is slow (24 hours for 10% of 125I-UK by plasma clot). In 4 patients plasma clearance of 125I-UK was essentially similar to that in rabbits. From the results obtained optimal dosage regimen of UK administration for complete thrombolysis in vivo was discussed.
D000368:Aged; D000818:Animals; D001777:Blood Coagulation; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D005343:Fibrinolytic Agents; D006801:Humans; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D013924:Thrombophlebitis / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
D005343:Fibrinolytic Agents; D007457:Iodine Radioisotopes; D010450:Endopeptidases; D014568:Urokinase-Type Plasminogen Activator