Lau K, DeFronzo R, Morrison G, Rascoff J, Goldberg M, Agus Z S
J Clin Pharmacol. 1976 Oct;16(10 Pt 1):489-97.
A double-blind crossover study was undertaken to delineate the renal tubular sites of action of bumetanide and to compare its effects upon electrolyte excretion to that of furosemide in six nephrotic patients with various degrees of renal insufficiency. Bumetanide was found to be a potent oral natriuretic agent without producing changes in either GFR or effective renal plasma flow. The natriuresis was associated with inhibition of proximal tubular transport as evidenced by an increased distal delivery (CH2O+CNA+K) and inhibition of sodium transport in the loop of Henle as shown by a fall in CH2O/CH2O+CC1 during sustained water diuresis and an unchanged TCH2O with continued hydropenia. The increases in free-water clearance induced by furosemide and bumetanide were equivalent, but bumetanide produced significantly higher flow rate, greater solute delivery from the proximal tubule, and a greater natriuresis. The data indicate that at the dosages used, bumetanide has a proportionately greater inhibitory effect than furosemide in both the proximal tubule and the ascending limb of the loop of Henle.
开展了一项双盲交叉研究,以明确布美他尼的肾小管作用部位,并比较其对6例不同程度肾功能不全的肾病患者电解质排泄的影响与呋塞米的影响。结果发现布美他尼是一种强效口服利钠剂,不会引起肾小球滤过率(GFR)或有效肾血浆流量的改变。利钠作用与近端肾小管转运受抑制有关,这可通过远端输送量(CH2O+CNA+K)增加得以证明,而在持续水利尿期间,CH2O/CH2O+CC1下降以及在持续低血容量状态下总CH2O不变,这表明髓袢升支粗段钠转运受到抑制。呋塞米和布美他尼诱导的自由水清除率增加相当,但布美他尼产生的流速显著更高,近端小管溶质输送量更大,利钠作用更强。数据表明,在所使用的剂量下,布美他尼在近端小管和髓袢升支粗段比呋塞米具有更大的抑制作用。