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 ¹²⁵I-E-6010 in Comparison with ¹²⁵I-Recombinant Tissue-Type Plasminogen Activator (rt-PA)

Abstract

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.