ABSORPTION, DISTRIBUTION, METABOLISM AND EXCRETION OF A NEW, C-14-LABELED OXAZOLIDINONE MAO-A INHIBITOR IN RAT AND DOG

1. After oral administration of C-14-labelled )benzothiazol-6-yl]-5-me toxymethyl-2-oxazolidinone (E2011) at a dose of 1 mg/kg, the blood lev el of radioactivity leached a maximum concentration (C-max) of 0.545 m u g eq./ml after 0.25 h in the rat and of 0.900 mu g eq./ml after 0.5 h in the dog. In dog plasma, C-max for radioactivity and unchanged E20 11 were 0.862 mu g eq./ml and 0.650 mu g/ml respectively with correspo nding T-max (time at C-max) of 0.75 and 0.25 h. The unchanged drug in dog plasma was below the detection limit (5 ng/ml plasma) after 24 h. 2. The tissue levels of radioactivity were measured at 0.25 (T-max), 6 , 24, and 168 h after administration to the rat and at 0.5 (T-max), 24 , and 168 h in the dog. The radioactivity was distributed in all tissu es examined at T-max in the rat and dog. The radioactivity levels of t he cerebral cortex in the rat and dog were 26 and 36% of the plasma le vel at T-max. The radioactivity in tissues decreased at almost the sam e rate as that in plasma. Plasma protein binding of the unchanged drug in the rat in vitro were about 70% in the range of 0.1-10 mu g/ml, an d those in the dog were about 45 % in the same concentration range. 3. Cumulative excretion of radioactivity in the rat was 74.5 % in urine and 22.5 % in faeces after 7 days. In the dog, 55.5 and 36.5 % of the radioactivity administered were excreted in urine and faeces respectiv ely after 7 days. The biliary excretion of radioactivity in the cannul ated rat was 23.0% within 48 h. 4. In tie analysis of plasma and tissu es of the rat and dog, the radioactivity for the unchanged drug was mu ch higher than metabolites. In tie analysis of urine, the same metabol ites were detected in the rat and dog, and the radioactivity of a meta bolite, IM1, was the highest in the both animals. Eight metabolites we re detected in the plasma, tissues and excreta of the rat, and four me tabolites in the dog. 5. In conclusion, the absorption, distribution, metabolism and excretion of C-14-labelled E2011 in the rat and dog hav e been established, and only minor differences were observed between t hese species.