METABOLISM OF 8-CHLORO-6-(ORTHO-CHLOROPHENYL)-1-METHYL-4H-S-TRIAZOLO [4,3-A] [1,4]BENZODIAZEPINE, TRIAZOLAM, A NEW CENTRAL DEPRESSANT .2. IDENTIFICATION AND DETERMINATION OF METABOLITES IN RATS AND DOGS

1. Eight metabolites of triazolam have been identified, namely, triazolam, dichloro-triazolobenzophenone (DCTB), 1'-hydroxytriazolam, dichloro-αhydroxytriazolobenzo-phenone (1'-hydroxy-DCTB), Ar-hydroxytriazolam, 4-hydroxytriazolam, Ar-1'-dihydroxytriazolam and 1',4-dihydroxytriazolam. 2. Major metabolites found in the urine were 1',4-dihydroxytriazolam, 1'-hydroxy-DCTB and DCTB m rats; 1'-hydroxytriazolam, 4-hydroxytriazolam and conjugated 1'-hydroxytriazolam in dogs. 3. Major metabolites found in the faeces were 4-hydroxytriazolam in rats; 1'-hydroxytriazolam and 4-hydroxytriazolam in dogs. 4. Conjugated 4-hydroxytriazolam was the major metabolite in both the original and reabsorbed bile of rats. 5. Major metabolites in free form in the plasma were 4-hydroxytriazolam and 1'-hydroxytriazolam in rats; triazolam and 1'-hydroxytriazolam in dogs. 6. The major metabolite in the brain was triazolam, but those in the liver were 4-hydroxytriazolam and triazolam, and in the kidneys were 4-hydroxytriazolam and 1',4-dihydroxytriazolam. 7. Major metabolites in the urine, faeces, plasma ard brain after 7-, 14- or 21-day repeated dosing in rats were not much different in type and ratio from those after single dosing. 8. Unchanged triazolam and 1'-hydroxytriazolam were the major metabolites in the plasma, placenta, foetus and amniotic fluid in pregnant rats. 9. There was no change in hepatic aniline hydroxylase and aminopyrine-N-demethylase activity from controls in rats given oral dose of [14C]triazolam for 14 days. © 1979 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.