Abstract
Blood concentration, distribution, metabolism and excretion of 14C-T-593 were investigated during and after repeated oral administration to male rats at a dose of 10 mg/kg for 21 days. In addition, the effects of T-593 on hepatic drug metabolizing enzyme system were also examined after repeated oral administration to male rats at the doses of 10, 30 and 100 mg/kg for 7 days.
1. The blood levels of radioactivity at 24 hr after daily dosing increased in parallel with the number of dosing. The blood level after the 21st dosing was 5.8 times higher than that after the 1st dosing.
2. The radioactivity levels in plasma and most tissues at 24 hr after the 1st, 7th, 14th and 21st dosing reached a steady state by the 14th dosing. The levels in the blood cells, hypophysis and testis after the 21st dosing decreased slowly compared with those after the 1st dosing.
3. Most of the radioactivity in the urine excreted within 24 hr after the 21st dosing consisted of the unchanged T-593 and the metabolic profile after the 21st dosing was similar to that after 1st dosing.
4. The cumulative excretion of radioactivity in the urine and feces within 24 hr after daily dosing was almost constant after the 2nd dosing. The cumulative excretion in the urine and feces within 96 hr after the 21st dosing was 1.09% and 96.35%, respectively.
5. Repeated dosing of T-593 had no effect on the drug metabolizing enzyme system in hepatic microsomes.
