Abstract
Blood levels and excretion of 3H-TTC-909, an oil-in-water (o/w) emulsion of isocarbacyclin methyl ester (3H-TEI-9090), after intravenous administration to rats were investigated in comparison with those of 3H-TEI-9090.
1. Blood levels of radioactivity in male rats after rapid intravenous injection of 3H-TTC-909 declined tri-phasically, with parameters (T1/2, AUC) which were almost similar to those for 3H-TEI-9090. The AUC increased in dose-dependent manner at the dose range of 0.5 to 8 μg/kg. In female rats, the AUC of blood level was about 1.8 times higher than that in male rats.
2. Isocarbacyclin (TEI-7165) levels in blood accounted for 11-15% of the total radioactivity by AUC, irrespective of dosage forms and administration mode (rapid injection/infusion).
3. Within 120 hr, 49.7% and 47.0% of the administered radioactivity was recovered in the urine and feces, respectively, after administration of 3H-TTC-909 to male rats. A similar excretion pattern was observed for 3H-TEI-9090. In female rats, urinary excretion after 3H-TTC-909 administration was about 10% higher than that in male rats.
4. In bile duct-cannulated male and female rats, 43.2% and 48.2% of the dose was excreted in the bile, respectively. Of the radioactivity excreted in the bile, 34.3% and 45.6% were reabsorbed from the intestinal tracts in male and female rats, respectively. This difference of reabsorption may be a cause of the higher blood levels found in female rats.
