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Dogs receiving a 7.5 mg/kg oral or i.v. dose of tritium labelled 9,9-dimethylacridane-10-carboxylic acid S-(2-dimethylamino)thiolethyl ester (DMA) as the methane sulfonate salt (DMA-MS) excreted 86-95% of the radioactivity within 6 days. A similar recovery was obtained for rats receiving 300 mg/kg orally of 15 mg/kg i.v. In both species, approximately 66% of the dose was excreted in the feces as metabolites. Absorption of the oral dose was shown to be 80% and 100% for the rat and dog, respectively. Up to 47% of an i.v. dose was excreted in the bile of rats and an efficient enterohepatic circulation process insues. The parent drug is rapidly metabolized in the tissues yielding at least 6 polar metabolites which contribute to relatively long plasma half-lives in the order of 40 h for dogs and 58-90 h for rats. An atypical increase in plasma radioactivity following an i.v. dose could be rationalized in view of these results. Metabolite profiles were examined in plasma, urine, bile and feces and found to be qualitatively similar. Des-methyl-DMA and DMA-N-oxide were identified as two minor metabolites.

The effects of in situ-produced oil shale retort water on the metabolism of various substrates was studied both in vivo and in vitro. The induction observed in rats was classified as Type I due to an increase in metabolism of hexobarbital and ethylmorphine without subsequent increases in zoxazolamine metabolism. The maximal absorption of the cytochrome-P450-CO complex was observed to be 450 millimicron, also consistent with Type I inducers. Cytochrome P-450 levels were also significantly increased over controls.

An in situ oil shale process water, designated Omega-9 water, was used in flow-through bioassays with fathead minnows, rainbow trout and rainbow trout eggs. Of the two fish species, rainbow trout were more sensitive to acute exposure to Omega-9 water with 96-hour LC50 dilutions of 0.51% and 0.41% in two independent determinations. In embryo-larval studies, the length of fry from eggs hatched and maintained in 0.16% process water was significantly less than that of eggs hatched in control water. A solution of the 13 major inorganic constituents of Omega-9 water, with a 96-hour LC50 of 0.56% for rainbow trout, showed that inorganics accounted for most of the acute toxicity of Omega-9 water.

3-Hydroxy-phenprobamate has been isolated from the urine of dogs and humans following oral administration of phenprobamate. The structure of this new metabolite was determined by analysis of its spectral data and corroborated by an unequivocal synthesis. The relative concentration of this substance, as well as other neutral metabolites occurring in the urine, either in the free form or as the glucuronide conjugates, is presented for both species. The presence of 3-hydroxy-phenprobamate in human plasma, and its interference with phenprobamate plasma level analysis by a previously described colorimetric method, is discussed