Species differences in the disposition and metabolism of 1-methyl-3-(3-pyridyl)-5-(2-hydroxy-methylphenyl)-1H-1,2,4-triazole, a potential sedative-hypnotic compound.
1. Disposition and metabolism of 1-methyl-3-(3-pyridyl)-5-(2-hydroxy-methylphenyl)-1H-1,2,4-triazole, a new sedative-hypnotic, were studied in rats (i.v. and p.o.), cats (i.v.) and human volunteers (p.o.) with 14C-labelled drug. 2. In rat and man, the compound is well absorbed, extensively metabolized, and excreted mostly through the kidney; it has short plasma half-lives, 0.6 h in rat, 0.9 h in man, and 1.9 h in cat. 3. In rat and man metabolism involves N-oxidation of the pyridine ring (Metabolite I), and in cat oxidation of the hydroxymethyl group (Metabolite II). Four other conjugated metabolites (III-VI) isolated from rat urine and bile, and from urine of cats and man, have been characterized. 4. The unchanged compound, but not its metabolites, crosses the blood-brain barrier in rat and cat. 5. The species differences in the disposition and metabolism of the compound are consistent with previous pharmacological data indicating a greater and more prolonged effect in cat.
D000328:Adult; D000818:Animals; D001646:Bile / Q000378:metabolism; D001711:Biotransformation; D001921:Brain / Q000378:metabolism; D002415:Cats; D005243:Feces / Q000032:analysis; D006801:Humans; D006993:Hypnotics and Sedatives / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014018:Tissue Distribution; D014230:Triazoles / Q000378:metabolism*
D006993:Hypnotics and Sedatives; D014230:Triazoles; C034437:1-methyl-3-(3-pyridyl)-5-(2-hydroxymethylphenyl)-1H-1,2,4-triazole