Puschett J B
J Clin Pharmacol. 1981 Nov-Dec;21(11):575-80. doi: 10.1002/j.1552-4604.1981.tb05666.x.
Upon administration of bumetanide in normal human subjects, both glomerular filtration rate and effective renal plasma flow were increased, in approximately proportional amounts. Sodium excretion rose to 16 per cent of filtered load, whereas there was a chloriuresis of 23 per cent. During maximal water diuresis, the drug caused an increase in urine flow rate associated with a rise in osmolal clearance and no change in solute-free water clearance. Intravenous injection of the drug during hypertonic saline infusion into hydropenic subjects resulted in the virtual abolition of water abstraction from the collecting duct. The drug caused a modest increase in phosphate excretion but no change in the percentage of filtered bicarbonate excreted. Furthermore, neither urinary pH nor net hydrogen ion excretion was altered by the drug. The data suggest that bumetanide has its major action in the loop of Henle but that it also inhibits sodium transport in the proximal tubule. In addition, the nature of the proximal action does not appear to be related to a carbonic anhydrase inhibitory effect. These latter observations regarding the proximal action of the drug were verified by micropuncture studies performed in the dog.
在正常人体受试者中给予布美他尼后,肾小球滤过率和有效肾血浆流量均增加,且增加幅度大致成比例。钠排泄量升至滤过负荷的16%,而氯利尿率为23%。在最大水利尿期间,该药物导致尿流率增加,同时渗透清除率升高,而无溶质水清除率无变化。在给缺水受试者静脉输注高渗盐水期间注射该药物,导致集合管对水的重吸收几乎完全消除。该药物使磷酸盐排泄略有增加,但滤过碳酸氢盐的排泄百分比无变化。此外,该药物既未改变尿液pH值,也未改变净氢离子排泄。数据表明,布美他尼的主要作用部位在髓袢,但它也抑制近端小管中的钠转运。此外,近端作用的性质似乎与碳酸酐酶抑制作用无关。关于该药物近端作用的这些观察结果在犬身上进行的微穿刺研究中得到了证实。