Bechtel W D, van Wayjen R G, van den Ende A
Arzneimittelforschung. 1986 Mar;36(3A):575-8.
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.
在4名健康受试者中口服单剂量的14C标记的溴替唑仑（2-溴-4-（2-氯苯基）-9-甲基-6H-噻吩并[3,2-f]-1,2,4-三唑并[4,3-a]-1,4-二氮杂卓，即我们的941，Lendormin）后，测量了血浆水平浓度、放射性的总排泄量以及未变化物质的血浆水平。[14C] - 溴替唑仑吸收迅速。血浆中放射性的消除半衰期为9.5小时，未变化的[14C] - 溴替唑仑的消除半衰期为4.4小时。使用二室开放模型，每天一次给予0.5毫克药物的给药方式未显示溴替唑仑及其代谢物有蓄积。在为期4天的研究中，64.9%的给予放射性经肾脏消除。总排泄量为剂量的86.5%。对经肾脏排泄的放射性进行提取和薄层色谱分离表明有两种主要代谢物，其中一种占主导。这些代谢物完全结合。未变化的[14C] - 溴替唑仑以少量排泄，低于剂量的2 - 3%。
