Hümpel M, Illi V, Milius W, Wendt H, Kurowski M
Eur J Drug Metab Pharmacokinet. 1979;4(4):237-43. doi: 10.1007/BF03189433.
The pharmacokinetics and metabolism of the new benzodiazepine lormetazepam were investigated in five male volunteers using the 14C-labelled drug (position 5). Lormetazepam was administered intravenously and orally, at a dose of 0.2 and 2 mg respectively, to each of the test subjects. Measurements of total radioactivity showed that the drug was absorbed completely and eliminated almost exclusively by the renal route. Maximum plasma level of active ingredient and total radioactivity were observed about 2 hours and 5 hours following oral administration. As early as 30 min following oral administration, concentration of active ingredient amounted to 80% of the maximum values. After both treatments the terminal half-life of total radioactivity and lormetazepam glucuronide in plasma corresponded to the half-life of elimination in urine of about 13 hours. After enzymatic hydrolysis with beta-glucuronidase/arylsulphatase, an average of 90% of total radioactivity from various urine and plasma samples was extractable with ether. Extracts from plasma contained only unchanged drug, indicating free and conjugated lormetazepam as ingredients of total radioactivity. Extracts from urine could be separated into lormetazepam and its N-demethylation derivative lorazepam. The relative amount of excreted lorazepam conjugate was demonstrated to be time-dependent, probably due to enterohepatic circulation. Since less than 6% of the total dose was demethylated by both routes of administration, it can be assumed that lormetazepam is the active product.
使用14C标记的药物（标记于5位），在5名男性志愿者中研究了新型苯二氮䓬类药物氯美扎酮的药代动力学和代谢情况。分别以0.2毫克和2毫克的剂量向每位受试对象静脉注射和口服氯美扎酮。总放射性测量结果表明，该药物被完全吸收，且几乎完全通过肾脏途径消除。口服给药后约2小时和5小时分别观察到活性成分的最大血浆水平和总放射性。口服给药后30分钟，活性成分浓度即达到最大值的80%。两种给药方式后，血浆中总放射性和氯美扎酮葡萄糖醛酸苷的终末半衰期与尿液消除半衰期相当，约为13小时。用β-葡萄糖醛酸酶/芳基硫酸酯酶进行酶水解后，各种尿液和血浆样品中平均90%的总放射性可用乙醚提取。血浆提取物中仅含有未变化的药物，表明游离和结合的氯美扎酮是总放射性的成分。尿液提取物可分离为氯美扎酮及其N-去甲基化衍生物劳拉西泮。排泄的劳拉西泮结合物的相对量显示出与时间相关，可能是由于肝肠循环。由于两种给药途径使总剂量中甲基化的比例均低于6%，因此可以认为氯美扎酮是活性产物。
