COMPARISON OF LOOP DIURETICS IN PATIENTS WITH CHRONIC RENAL-INSUFFICIENCY
COMPARISON OF LOOP DIURETICS IN PATIENTS WITH CHRONIC RENAL-INSUFFICIENCY
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DOI：
10.1038/ki.1987.246
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发表时间：
1987-10-01
影响因子：
19.6
通讯作者：
BRATER, DC
中科院分区：
文献类型：
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作者：
VOELKER, JR;CARTWRIGHTBROWN, D;BRATER, DC
呋塞米和布美他尼具有许多共同特征，包括降低氮质血症患者的利尿钠作用。据推测，这种情况对每种药物的影响是相同的。然而，之前的研究表明，其到达作用部位的途径不同。尽管未经严格测试，但这种潜在的差异可能会导致它们在氮质血症中使用时有所不同。因此，我们在一项随机交叉研究中，在控制钠摄入期间，评估了 10 名稳定慢性肾功能不全（平均肌酐清除率 = 14.1 ± 2.0 ml/min/1.73 m2）成年患者静脉注射呋塞米和布美他尼的药代动力学和药效学特征。我们的目标是评估利尿效果的差异，并以此确定产生最大反应所需的剂量。速尿和布美他尼的平均利尿剂量分别为 172 毫克和 4.3 毫克（比例 = 40:1），足以产生最大反应。尽管钠的最大排泄分数相似（呋塞米为 18.2 .+-. 2.6%，布美他尼为 19.4 .+-. 4.5%，P = 0.687），表明两种药物的肾小管反应性相同，但通过在最初 8 小时内累积尿钠排泄量化的总体反应，呋塞米高出 52%（108 .+-. 4.5%，布美他尼为 19.4 .+-. 4.5%）。 17 与 71 .+-.P = 0.042)。钠排泄总量的差异是由于布美他尼的非肾脏清除率保持不变（呋塞米为 113.+-.12，而呋塞米为 53.+-.4ml/min，P = 0.001），这导致血清中可输送到尿液中的布美他尼相对较少。因此，虽然肾脏清除率在数值上相似（呋塞米和布美他尼分别为 6.+-.1 与 7.+-.1 ml/min，P = 0.549），但在最初 8 小时内尿液中排泄的布美他尼剂量百分比比呋塞米低 42%（5.2.+-.1.0% 与 9.0.+-.1ml/min）。 1.8%，P = 0.021）。总之，与肾功能正常患者等效的布美他尼剂量相比，稳定的严重慢性肾功能不全患者静脉注射呋塞米后的累积钠排泄量更高。两种利尿剂之间差异的机制可以通过非肾脏清除率的差异来解释。这些发现的临床意义是，类似的患者需要 20:1 的呋塞米与布美他尼剂量比才能获得相同的效果，而肾功能保留的患者则需要 40:1 的剂量比。
Furosemide and bumetanide share a number of characteristics including reduced natriuretic effects in azotemic patients. It has been presumed that this condition affects each drug equally. Previous studies, however, suggest dissimilar pathways of delivery to their sites of action. Though not rigorously tested, this potential disparity might cause them to differ when used in azotemia. We, therefore, assessed the pharmacokinetic and pharmacodynamic characteristics of intravenously administered furosemide and bumetanide in ten adult patients with stable, chronic renal insufficiency (mean creatinine clearance = 14.1 .+-. 2.0 ml/min/1.73 m2) in a randomized, cross-over study during controlled sodium intake. Our goals were to assess differences in diuretic effectiveness and in so doing to determine the dose required to produce a maximal response. The mean diuretic doses of 172 and 4.3 mg for furosemide and bumetanide, respectively (ratio = 40:1) were sufficient to produce a maximum response. Despite similarities in maximal fractional excretion of sodium (18.2 .+-. 2.6% with furosemide vs. 19.4 .+-. 4.5% with bumetanide, P = 0.687) demonstrating an equal tubular respnsiveness to both drugs, overall response as quantified by cumulative natriuresis in the initial eight hour period was 52% greater with furosemide (108 .+-. 17 vs. 71 .+-. 7 mEq; P = 0.042). The difference in total excreted sodium was accounted for by a preserved nonrenal clearance of bumetanide (113 .+-. 12 compared to 53 .+-. 4 ml/min for furosemide, P = 0.001) which resulted in relatively less bumetanide in serum available to be delivered into the urine. Thus, while renal clearances were numerically similar (6 .+-. 1 vs. 7 .+-. 1 ml/min for furosemide and bumetanide, respectively, P = 0.549), the percentage of the bumetanide dose excreted in the urine during the initial eight hours was 42% less than furosemide (5.2 .+-. 1.0% vs. 9.0 .+-. 1.8%, P = 0.021). In summary, patients with stable, severe chronic renal insufficiency have a greater cumulative sodium excretion after intravenous furosemide compared to a dose of bumetanide determined to be equipotent in patients with normal renal function. The mechanism of the disparity between the two diuretics was explained by differences in nonrenal clearance. The clinical implications of these findings are that comparable patients require a dose ratio of furosemide to bumetanide of 20:1 to attain equal effects in contrast to a ratio of 40:1 in patients with preserved renal function.