MECHANISM OF FUROSEMIDE RESISTANCE IN ANALBUMINEMIC RATS AND HYPOALBUMINEMIC PATIENTS
MECHANISM OF FUROSEMIDE RESISTANCE IN ANALBUMINEMIC RATS AND HYPOALBUMINEMIC PATIENTS
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DOI：
10.1038/ki.1987.192
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发表时间：
1987-08-01
影响因子：
19.6
通讯作者：
MORINO, Y
中科院分区：
文献类型：
--
作者：
INOUE, M;OKAJIMA, K;MORINO, Y
为探讨低白蛋白血症患者对速尿产生抵抗的机制，本文观察了速尿对正常大鼠、无白蛋白血症大鼠（NAR）及低白蛋白血症患者尿量的影响。静脉注射速尿可迅速增强正常大鼠的钠利尿作用，但对NAR无明显影响。总血浆清除率和分布容积的呋塞米在NAR比在正常大鼠大得多，而没有观察到这些药物动力学参数的两个动物组之间的利尿剂的未结合分数的显着差异。相比之下，尿中速尿分泌量显着低于在NAR比正常大鼠。注射呋塞米与白蛋白结合可显著促进NAR患者的利尿作用，而相同剂量的白蛋白单独给药无作用，表明与白蛋白结合对于呋塞米向肾脏（其作用部位）的递送至关重要。注射复合物迅速增加尿量的低白蛋白血症患者谁表现出显着的阻力，这种利尿剂。因此，NAR和低白蛋白血症患者对呋塞米的耐药可以在相同的基础上解释。
To elucidate the mechanism of resistance of hypoalbuminemic patients to furosemide, the effect of the diuretic on urine volume of normal and analbuminemic rats (NAR) and of hypoalbuminemic patients was studied. Intravenous administration of furosemide rapidly enhanced sodium diuresis in normal rats but not in NAR. Total plasma clearance and distribution volume of furosemide were much larger in NAR than in normal rats, while no significant difference in these pharmacokinetic parameters was observed for the unbound fraction of the diuretic between the two animal groups. In contrast, urinary secretion of furosemide was significantly lower in NAR than in normal rats. Injected furosemide bound to albumin markedly promoted diuresis in NAR, while the same dose of albumin alone had no effect, indicating that binding to albumin is essential for the delivery of furosemide to the kidney, the site for its action. Injection of the complex rapidly increased the urine volume of hypoalbuminemic patients who showed a marked resistance to this diuretic. Thus, the resistance to furosemide in both NAR and hypoalbuminemic patients may be explained on the same basis.