Studies on the Metabolic Fate of a New Thromboxane A₂ Receptor Antagonist, S-1452 (II) : Distribution and Excretion after Single and Repeated Oral Administration to Rats

Abstract

The tissue distribution and excretion of S-1452 were studied in rats after a single and repeated oral administration of ¹⁴C-S-1452 at a dose of 5mg/kg or 5mg/kg/day for 10 days.
1. The level of radioactivity in the liver was markedly higher than those in other tissues after both single and repeated dosing.
2. Whole body autoradiography after a single or repeated administration demonstrated that the radioactivity in the hepatic vein was markedly weaker than that in the portal vein. This phenomenon suggests that the hepatic first-pass effect of (+)-S-145 in rats was the extensive one.
3. The daily excretions of radioactivity in urine and feces were constant during repeated administration. Within 168hr after the last dosing, 8.3% and 89.2% of the administered radioactivity were recovered from the urine and feces, respectively.
4. After both single and repeated administration, the radioactivity tended to disappear slowly from the whole blood, spleen and bone marrow.
5. After repeated administration of ¹⁴C-S-1452 for 10 days, no accumulation of radioactivity in the tissues was observed.