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

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Abstract
Disposition and metabolism of 1-methyl-3-(3-pyridyl)-5-(2-hydroxymethylphenyl)-1H-1,1,2,4-triazole, a new sedative-hypnotic, were studied in rats (i.v. and orally), cats (i.v.) and human volunteers (used) with 14C-labeled drug. 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. In rat and man, metabolism involves N-oxidation of the pyridine ring, and in cat oxidation of the hydroxymethyl group. Four other conjugated metabolites isolated from rat urine and bile and from urine of cats and man were characterized. The unchanged compound, but not its metabolites, crossed the blood-brain barrier in rat and cat. 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.