Bartoli E, Arras S, Faedda R, Soggia G, Satta A, Olmeo N A
J Clin Pharmacol. 1980 Jul;20(7):452-8. doi: 10.1002/j.1552-4604.1980.tb01718.x.
Experiments were performed on humans to study the blunting on the diuretic action of furosemide by prostaglandin synthetase inhibitors. Maximal water diuresis was instituted. At the peak of urine flow, clearance periods were performed during baseline conditions and repeated after the injection of aspirin and, subsequently, of furosemide. Control subjects did not receive aspirin. Urine flow rate (V), Cosm, and Na excretion (UNa) . V were significantly lower when the administration of the diuretic had been preceded by that of aspirin. In the absence of furosemide, however, aspirin did not influence renal hemodynamics nor Na and water reabsorption. Therefore, the same experimental protocol was repeated in paired experiments where each normal subject served as his own control, being studied twice, in the presence and absence of aspirin, respectively. The average changes in water and Na excretion induced by furosemide were not different when the patients were pretreated with aspirin as compared with those measured in the absence of prostaglandin inhibition. Changes occurring in individual experiments were significantly correlated (r = 0.95, P less than 0.01) with those in calculated furosemide clearance. Since aspirin, indomethacin, and meclophenamate are secreted by the organic acid transport system of the proximal tubule, competition for a common secretory mechanism, rather than prostaglandin inhibition, could mediate the blunting of furosemide diuresis.
进行了人体实验，以研究前列腺素合成酶抑制剂对呋塞米利尿作用的抑制。采用最大水利尿法。在尿流峰值时，分别在基线条件下以及注射阿司匹林后、随后再注射呋塞米后进行清除期实验。对照受试者未服用阿司匹林。当在给予利尿剂之前先给予阿司匹林时，尿流率（V）、菊粉清除率（Cosm）和钠排泄量（UNa）.V显著降低。然而，在没有呋塞米的情况下，阿司匹林并不影响肾血流动力学以及钠和水的重吸收。因此，在配对实验中重复相同的实验方案，每个正常受试者作为自己的对照，分别在有和没有阿司匹林的情况下进行两次研究。与在没有前列腺素抑制的情况下测量的结果相比，当患者用阿司匹林预处理时，呋塞米引起的水和钠排泄的平均变化没有差异。个别实验中发生的变化与计算的呋塞米清除率的变化显著相关（r = 0.95，P小于0.01）。由于阿司匹林、吲哚美辛和甲氯芬那酸是由近端小管的有机酸转运系统分泌的，对共同分泌机制的竞争，而非前列腺素抑制，可能介导了呋塞米利尿作用的减弱。
