The absorption, distribution, metabolism and excretion of Oxiracetam (CT-848) were studied in male rats during and after the consecutive oral administration of 10mg/kg of 14C-CT-848 for 14 days. 1. The plasma concentrations of radioactivity at 1hr and 6hr after each dose were not affected by repeated administration. After the 14th doses, radioactivity in plasma reached Cmax at 1hr and decreased with a half-life of 1.6hr (2 ?? 8 hr). 2. The concentrations of radioactivity in tissues at 6hr were not significantly different between after 7th and 14th doses and 1st dose. The elimination of radioactivity from tissues was rapid after the 14th dose. Accumulation of radioactivity in tissues was not observed. 3. The extents of excretion in urine and feces during consecutive oral do sing were 27.2 ?? 31.3%, and 52.7?? 72.1%, respectively. The elimination of radioactivity from the body was completed by 48hr after the final administration. 4. After repeated oral administration to non-fasting male rats, only unchanged compound was observed in plasma at 1hr and 6hr. In urine and feces up to 24hr after 1st and 14th doses only about 1 % of the recovered radioactivity was corresponded to unknown metabolites and the remainder was unchanged compound.
The transfer into fetus, milk and tumor of a benzoylphenylurea derivative, HO-221 was studied after oral administration of 14C(Pc) HO-221 to rats at a dose of 25 mg/kg. The radioactivity levels in the fetuses on the 12th and 18th days of gestation were 35 and 67% of those in the maternal plasma, respectively. The radioactivity level in the fetus on the 12th day of gestation was below the detection limit at 48 hr after administration. The radioactivity levels in the fetal tissues, except the intestinal contents, on the 18th day of gestation were less than 14% of the maximum. The radioactivity level in the milk was 3-4 times higher than that in the plasma up to 12 hr after administration. The elimination of radioactivity from the milk was more rapid than from the plasma. The radioactivity level in the tumor was similar to that in the plasma. No difference was noted in the distribution of radioactivity into the tissues and the excretion of radioactivity in the urine and feces between tumor bearing and normal male rats.
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