Blood level, excretion, and metabolite pattern of [14C]-brotizolam in humans.

Following a single oral dose of 14C-labeled brotizolam (2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3, 2-f]-1,2,4-triazolo[4,3-a]-1,4-diazepine. We 941, Lendormin) the plasma level concentration and the total excretion of the radioactivity as well as the plasma level of the unchanged substance was measured in 4 healthy subjects. [14C]-Brotizolam was rapidly absorbed. The elimination half-life of the radioactivity from the plasma was 9.5 h, that of the unchanged [14C]-brotizolam 4.4 h. Using a two-compartment open model, the stimulation of giving 0.5 mg of the drug once daily showed no accumulation of brotizolam and its metabolites. Within the 4-day study 64.9% of the given radioactivity was eliminated renally. The total excretion was 86.5% of the dose. Extraction and thin layer chromatographic fractionation of the renally excreted radioactivity indicated two major metabolites one of which predominated. The metabolites were completely conjugated. Unchanged [14C]-brotizolam was excreted in minor amounts below 2-3% of the dose.