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Blood or plasma concentration, distribution, metabolism and excretion of E6010 were studied in male rats after a single intravenous administration of 125I-E6010 in comparison with 125I-rt-PA. 1. After a single intravenous administration of 125I-E6010, plasma clearances of TCA-precipitable radioactivity, immunoreactivity, fibrinolytic activity and the unchanged E6010 were 10.3, 11.2, 3.1 and 5.5 times lower than those after dosing of 125I-rt-PA, respectively. In the plasma, the complexes of 125I-E6010 with α2-macroglobulin and with α2-plasmin inhibitor were observed after dosing of 125I-E6010, as well as after dosing of 125I-rt-PA. 2. After a single intravenous administration of 125I-E6010, liver levels of TCA-precipitable radioactivity reached maximum level at 15 min after administration accounting for about 19% of administered radioactivity. In the case of 125I-rt-PA, it reached maximum level at 5 min accounting for about 54% of administered dose. These results suggest that the differences in the distribution to the liver between E6010 and rt-PA resulted in the difference of plasma clearances. 3. Within 7days after a single int ravenous administration of 125I-E6010, 96.05% and 5.32% of the administered radioactivity were excreted into urine and feces, respectively. Biliary excretion of radioactivity was 17.01% of the dose within 48hr after a single intravenous administration of 125I-E6010. Both radioactivity excreted in urine and in bile consisted almost of small molecular weight metabolites or free 125I.

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Studies on the Metabolic Fate of Modified Recombinant Tissue-Type Plasminogen Activator (E6010) (1): Blood or Plasma Concentration, Distribution, Metabolism and Excretion in Rats after a Single Intravenous Administration of l25I-E6010 in Comparison with l25I-Recombinant Tissue-Type Plasminogen Activator (rt-PA).