Abstract
The distribution of orally and intravenously administered 14C-oxazolam was studied in mice by means of whole-body autoradiography and in rats by scintillation counting of the organs and tissues. The radioactivity was found to be widely distributed in various tissues including the brain at 30 min after oral administration, reached the maximum levels within 1 hr and thereafter declined rather rapidly. The distribution patterns were similar for mice and rats, except that the brain uptake of the drug was appreciably higher in mice than in rats. A high affinity of oxazolam to the brain tissue was demonstrated by an extremely high and rapid uptake of radioactivity by the brain after intravenous injection in mice. The brain level reached its maximum at about 1 min after the injection and thereafter fell off rapidly, some retention of radioactivity being observed in the white matter of the brain-stem and in the trigeminal nerve. Autoradiographic studies in pregnant mice demonstrated that there is a slow and only a slight penetration of radioactivity through the placenta. A comparison of the excretion patterns of oxazolam after oral administration in mice, rats, dogs and man revealed that in mice and rats the excretion in the feces, mostly derived from the biliary excretion, was more important than that in the urine, while in dogs a larger part was excreted in the urine and in man the most part (ca. 80% of the dose) in the urine.
