Schwartz M A
J Clin Pharmacol. 1981 Nov-Dec;21(11):555-63. doi: 10.1002/j.1552-4604.1981.tb05664.x.
The metabolism of bumetanide is reviewed, with emphasis on the relationship between metabolism and diuretic activity. Substantial evidence has been obtained for the thesis that diuretic activity is dependent on the amount of bumetanide which reaches the renal tubule. Therefore, bumetanide is a potent diuretic in those species, e.g., human and dog, in which a substantial fraction of the administered dose is excreted as unchanged drug in the urine. In contrast, relatively weak diuretic activity is seen in the rat, a species which very effectively biotransforms bumetanide to inactive metabolites. The metabolites which have been identified in human and rat urine are presented, and the point is made that in both species metabolism of bumetanide appears to be limited to oxidation of the N-butyl side chain. Different (and unidentified) metabolites are excreted by the dog. A prominent metabolite formed in the dog, however, is the acylglucuronide of bumetanide, which was detected in plasma and bile but was not seen in urine or feces. Tissue distribution of bumetanide in the dog is presented so as to show the ability of the kidney to concentrate bumetanide. In the human, bumetanide disposition is also characterized by 95 per cent plasma protein binding and a plasma half-life of 1 to 2 hours. Attention is given to the possibility that the clinical response to bumetanide can be altered by factors which affect drug oxidation by the mixed-function oxygenase system; e.g., induction of the drug-metabolizing enzymes may lead to increased biotransformation of bumetanide and concomitant decreased diuretic activity.
本文综述了布美他尼的代谢情况，重点关注代谢与利尿活性之间的关系。有充分证据支持以下论点：利尿活性取决于到达肾小管的布美他尼的量。因此，在那些物种（如人和狗）中，布美他尼是一种强效利尿剂，在这些物种中，相当一部分给药剂量以原形药物形式从尿液中排泄出来。相比之下，在大鼠中观察到相对较弱的利尿活性，大鼠能非常有效地将布美他尼生物转化为无活性的代谢产物。介绍了在人和大鼠尿液中已鉴定出的代谢产物，并指出在这两个物种中，布美他尼的代谢似乎仅限于N - 丁基侧链的氧化。狗排泄的是不同的（且未鉴定的）代谢产物。然而，在狗体内形成的一种主要代谢产物是布美他尼的酰基葡萄糖醛酸苷，在血浆和胆汁中检测到了它，但在尿液或粪便中未发现。展示了布美他尼在狗体内的组织分布情况，以显示肾脏浓缩布美他尼的能力。在人体内，布美他尼的处置还具有95%的血浆蛋白结合率和1至2小时的血浆半衰期。文中还关注了影响混合功能氧化酶系统对药物氧化的因素可能改变对布美他尼的临床反应的可能性；例如，药物代谢酶的诱导可能导致布美他尼的生物转化增加，同时利尿活性降低。
