Studies on the Metabolism of Oxazolam. III. Absorption from Rat Intestine and Metabolites in the Liver, Brain and Blood

The intestinal absorption of 14C-oxazolam was studied by means of rat ligated loop technique and the metabolites in the intestine, liver, blood and brain were followed by thin-layer chromatography. The results indicated that oxazolam is very easily absorbed from almost whole part along the rat intestine, with the fastest rate from the upper part of the small intestine and is transferred from the lumen into the blood stream mostly in the form of unaltered oxazolam. It was also clarified that a large part, approximately 60%, of the drug absorbed is brought back into the intestinal lumen through the biliary excretion and the extent of occurring its reabsorption appears to be insignificant. In the brain, oxazolam was the main component of the radioactivity at the earliest period after the administration, while N-desmethyldiazepam showed a gradual increase with increasing the time concomitant with a decline of the oxazolam level, reaching a maximum at a later period. A possible participation of this metabolite for the duration of anticonvulsant activity of oxazolam was pointed out. It was suggested from in vitro studies that N-desmethyldiazepam was derived from its gradual transfer from the blood circulation into the brain tissue after being formed from oxazolam in the liver microsomal enzyme.