Triazolam disposition

Triazolam (T) is a new, potent hypnotic with a short duration of action in man. After an 0.88‐mg oral dose of T‐ 14 C in six male subjects, mean recovery of 14 C radioactivity was 85% in urine and 8% in feces. The major urinary metabolites were α‐hydroxytriazolam (α‐HT) and 4‐hydroxytriazolam (4‐HT), accounting for 69% and 11% of the urinary 14 C, and these were mostly in conjugated form. α,4‐Dihydroxytriazolam and three dichlorotriazolylbenzophenone analogs were minor metabolites. At least 85% of the dose was rapidly absorbed; mean absorption half‐life (t½ A ) was 2.8 min. After reaching a mean peak plasma level (C max ) of 8.8 ng/ml at mean time (t max ) of 1.3 hr, plasma T decreased rapidly with a mean elimination half‐life (t½ E ) of 2.3 hr. The remainder of the plasma 14 C consisted predominantly of glucuronides of α‐HT and 4‐HT. Mean plasma parameters for these metabolites were as follows: α‐HT‐glucuronide, t½ E = 3.9 hr, t max = 1.3 hr, C max = 6.1 ng/ml; 4‐HT‐glucuronide, ½ E = 3.8 hr, t max = 2.5 hr, C max = 6.1 ng/ml. Nonconjugated α‐HT and 4‐HT were present in plasma but in insufficient amounts for kinetic analysis. The results are consistent with the short duration of action. Clinical Pharmacology and Therapeutics (1981) 29, 81–93; doi: 10.1038/clpt.1981.14