Myers J B, Gillies A, Waga S, Morgan T O
Br J Clin Pharmacol. 1980 Oct;10(4):345-51. doi: 10.1111/j.1365-2125.1980.tb01770.x.
A double-blind comparison of the effect of tienilic acid (250 mg) and amiloride (5 mg) on renal function in healthy volunteers and of tienilic acid plus amiloride compared to hydrochlorothiazide (50 mg) plus amiloride in patients with mild to moderate essential hypertension for safety and hypotensive efficacy was made. Renal plasma flow ([I] iodohippurate clearance) and glomerular filtration rate ([I] iothalamate clearance and 24 h creatinine clearance) were not affected by tienilic acid or amiloride alone or in combination despite a rise in plasma urea and plasma creatinine (within the normal range) in healthy volunteers. In hypertensive patients tienilic acid and tienilic acid plus amiloride treatments caused a rise in plasma urea and plasma creatinine similar to hydrochlorothiazide and hydrochlorothiazide plus amiloride but no significant change in creatinine clearance occurred with any of the treatments. Tienilic acid and hydrochlorothiazide caused hypokalaemia in the patients which was normalized by addition of amiloride. Fewer subjects became hypokalaemic when amiloride was added to tienilic acid than when tienilic acid was given alone. The antihypertensive effect of tienilic acid and tienilic acid plus amiloride was similar to hydrochlorothiazide and hydrochlorothiazide plus amiloride in patients with hypertension. No effect on blood pressure was observed in the healthy volunteers. Plasma uric acid was significantly reduced by tienilic acid alone and in combination in patients and subjects whereas a significant elevation occurred with hydrochlorothiazide. Side effects were increased when amiloride was added to either tienilic acid or hydrochlorothiazide, but side effects were less common after treatment with tienilic acid than following hydrochlorothiazide. The combination of tienilic acid plus amiloride significantly reduces blood pressure and appears to be well tolerated with no adverse effects on renal function or plasma potassium in patients with mild to moderate hypertension and normal renal function. Addition of amiloride may be useful if hypokalaemia occurs following tienilic acid therapy in such patients.
进行了一项双盲比较，研究替尼酸（250毫克）和阿米洛利（5毫克）对健康志愿者肾功能的影响，以及在轻度至中度原发性高血压患者中，将替尼酸加阿米洛利与氢氯噻嗪（50毫克）加阿米洛利相比较的安全性和降压效果。单独使用替尼酸或阿米洛利，或二者联合使用，均未影响健康志愿者的肾血浆流量（[I]碘马尿酸盐清除率）和肾小球滤过率（[I]碘他拉酸盐清除率和24小时肌酐清除率），尽管健康志愿者的血浆尿素和血浆肌酐有所升高（在正常范围内）。在高血压患者中，替尼酸和替尼酸加阿米洛利治疗导致血浆尿素和血浆肌酐升高，与氢氯噻嗪和氢氯噻嗪加阿米洛利相似，但任何一种治疗方法均未使肌酐清除率发生显著变化。替尼酸和氢氯噻嗪导致患者低钾血症，加入阿米洛利后低钾血症得以纠正。与单独使用替尼酸相比，替尼酸加阿米洛利时出现低钾血症的受试者较少。在高血压患者中，替尼酸和替尼酸加阿米洛利的降压效果与氢氯噻嗪和氢氯噻嗪加阿米洛利相似。在健康志愿者中未观察到对血压的影响。单独使用替尼酸及其联合使用时，患者和受试者的血浆尿酸均显著降低，而氢氯噻嗪则导致血浆尿酸显著升高。当阿米洛利加入替尼酸或氢氯噻嗪时，副作用会增加，但替尼酸治疗后的副作用比氢氯噻嗪后更少见。替尼酸加阿米洛利的组合可显著降低血压，对于轻度至中度高血压且肾功能正常的患者，似乎耐受性良好，对肾功能或血钾无不良影响。如果此类患者在替尼酸治疗后出现低钾血症，加入阿米洛利可能会有用。
