Vitiello B, Buniva G, Bernareggi A, Assandri A, Perazzi A, Fuccella L M, Palumbo R
Int J Clin Pharmacol Ther Toxicol. 1984 May;22(5):273-7.
Premazepam, a pyrrolodiazepine with potential anxiolytic properties, behaves as a partial antagonist to diazepam in animal tests. Its pharmacokinetics and metabolism were studied in four healthy volunteers. After oral administration of 30 mg [6-14C] premazepam, the plasma levels of total radioactivity reached maximum concentrations 1-4 h (mean 2 h) following administration. The plasma curve was described by an open one-compartment model, and half-life was 11.5 +/- 1.3 h. Levels of the unchanged compound accounted for about 80% of the total radioactivity up to 24 h. Half-life of the unchanged compound was 7.9 +/- 1.2 h. On the average, 89.6% of the administered radioactivity was recovered in the urine and 2.3% in the feces during the 5 days following administration. Unchanged premazepam accounted for about 70% of the total radioactivity excreted in the urine. Of the three metabolites identified in the urine, none was active in vitro in displacing 3H-diazepam from its forebrain receptors in the rat, indicating that only the parent compound has definite pharmacologic activity.
普瑞马西泮是一种具有潜在抗焦虑特性的吡咯并二氮杂䓬，在动物试验中表现为地西泮的部分拮抗剂。在四名健康志愿者身上研究了其药代动力学和代谢情况。口服30毫克[6-14C]普瑞马西泮后，血浆总放射性水平在给药后1 - 4小时（平均2小时）达到最高浓度。血浆曲线可用开放的一室模型描述，半衰期为11.5±1.3小时。在24小时内，未变化化合物的水平约占总放射性的80%。未变化化合物的半衰期为7.9±1.2小时。给药后5天内，平均89.6%的给药放射性在尿液中回收，2.3%在粪便中回收。未变化的普瑞马西泮约占尿液中排泄的总放射性的70%。在尿液中鉴定出的三种代谢物中，没有一种在体外能使大鼠前脑受体上的3H-地西泮移位，这表明只有母体化合物具有明确的药理活性。
