Disposition of triazolam, 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo[4,3-a]benzodiazepine, in the dog.
Disposition of triazolam (T), a new, potent, hypnotic agent, was studied in the dog. A single 0.5-mg/kg oral or iv dose of 14C-labeled T was rapidly absorbed, and although 88% was bound to serum proteins, T levels decreased with a half-life of 0.85 hr. Metabolism of T was rapid, with a first-pass effect observed after oral administration. Excretion of drug-related materials was rapid; urinary and fecal excretion of 14C were equal. Urine contained no measurable T, and metabolites were mostly conjugated. The major urinary metabolite was the alpha-HT analog of T, resulting from oxidation of the 1-methyl group of the triazole moiety. Other metabolites identified were the 4-hydroxy and alpha,4-hHT analogs of T, as well as the 1-demethyl analog, which probably results from further oxidation of alpha-hydroxy-T. Evidence also was obtained for two other monohydroxy analogs plus a dihydroxy, monohydroxymonomethoxy, and a dihydroxymonomethoxy analog of triazolam.
D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D004285:Dogs; D006900:Hydroxylation; D007275:Injections, Intravenous; D008297:Male; D011485:Protein Binding; D014229:Triazolam / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D001798:Blood Proteins; D014229:Triazolam