Metabolism of 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo [4,3-alpha] [1,4]benzodiazepine, triazolam, a new central depressant. II. Identification and determination of metabolites in rats and dogs.
1. Eight metabolites of triazolam have been identified, namely, triazolam, dichlorotriazolobenzophenone (DCTB), 1'-hydroxytriazolam, dichloro-alpha-hydroxytriazolobenzophenone (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 in 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 and 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.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001577:Benzophenones / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004285:Dogs; D005243:Feces / Q000032:analysis; D005260:Female; D005333:Fetus / Q000378:metabolism; D008297:Male; D008431:Maternal-Fetal Exchange; D008954:Models, Biological; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D013045:Species Specificity; D014018:Tissue Distribution; D014229:Triazolam / Q000378:metabolism* / Q000652:urine
D014151:Anti-Anxiety Agents; D001577:Benzophenones; D014229:Triazolam