A pharmacokinetics study on Oxiracetam in rats. (II): Plasma levels profile, tissue distribution, metabolism and excretion during and after the repeated oral administration.

Abstract

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.