Absorption, metabolism, and excretion of oxazepam and its succinate half-ester

C 14 -Oxazepam was administered orally to dogs, rats, and pigs. Radioassay of blood, various tissues, and excreta indicated that the drug was well absorbed. A single dose was largely eliminated within 2 days, mostly via urine in dogs and pigs and via feces in rats. One metabolite, a glucuronide, accounted for more than 95 per cent of the radioactivity of dog and pig urine. The radioactivity of rat urine was distributed among at least seven metabolites. C 14 -Labeled-Wy-4426 (a succinate half-ester of oxazepam) was found to disappear rapidly from an i.m. injection site in rats and to be distributed uniformly throughout the organs. Exceptions were the gastrointestinal tract, which appeared to be the route favored for excretion in this species, and the liver and kidney, in which somewhat higher than average levels were attained shortly after injection. About two-thirds of the dose was excreted in feces and about one-fifth in urine by the forty-eighth hour after injection. The drug appeared to undergo the same extensive metabolic alteration in rats as oxazepam—at least seven distinct metabolites appearing in urine. After i.v. injection of Wy-4426 in dogs, blood levels peaked within 15 minutes but declined slowly, so that even at 48 hours appreciable levels were found. The blood values from the fourth hour compared closely with those obtained following oral administration of oxazepam. Dogs excreted about two-thirds of the dose in urine and one-third in feces within 72 hours. Three radioactive spots in chromatographed urine of dogs injected with Wy-4426 were identified as unchanged drug, oxazepam, and the glucuronide of oxazepam. Similar spots were obtained when Wy-4426 was administered to pigs. The fate of oxazepam in humans was similar to that in dogs and pigs.