Dixey J J, Noormohamed F H, Lant A F, Brewerton D A
Br J Clin Pharmacol. 1987 Jan;23(1):55-63. doi: 10.1111/j.1365-2125.1987.tb03009.x.
We have studied the effect of a single dose challenge of naproxen (500 mg) and sulindac (200 mg) on renal function in five volunteers, and the effect of a single dose challenge of the thiazide, hydrochlorothiazide (100 mg), and loop diuretic, piretanide (6 mg) on renal function when the diuretics were given alone or when superimposed on chronic therapy of either naproxen or sulindac. None of the nonsteroidal anti-inflammatory drug (NSAID) or diuretic exposures significantly influenced glomerular filtration rate, as measured by creatinine clearance. Over the first 4 h of the study, both naproxen and sulindac reduced fractional excretion of sodium by approximately 50%. Sulindac also caused a significant uricosuria whilst naproxen promoted urate retention. Similar changes were observed over 8 h. Superimposition of either hydrochlorothiazide or piretanide on top of chronic sulindac therapy resulted in a blunting of the natriuresis by approximately 30% compared to when these diuretics were given alone: the action of the diuretics was unchanged by naproxen. Sulindac pretreatment did not alter the urinary excretion of either hydrochlorothiazide or piretanide; naproxen did not alter hydrochlorothiazide excretion. On the basis of these findings, it is concluded that NSAIDs exert direct tubular effects that do not necessarily interfere with the delivery of diuretics to their sites of action within the nephron.
我们研究了萘普生（500毫克）和舒林酸（200毫克）单次剂量激发对5名志愿者肾功能的影响，以及噻嗪类利尿剂氢氯噻嗪（100毫克）和袢利尿剂吡咯他尼（6毫克）单次剂量激发在单独给药或叠加于萘普生或舒林酸的慢性治疗时对肾功能的影响。通过肌酐清除率测量，非甾体抗炎药（NSAID）或利尿剂的暴露均未显著影响肾小球滤过率。在研究的最初4小时内，萘普生和舒林酸均使钠的分数排泄减少了约50%。舒林酸还导致显著的尿酸尿，而萘普生促进尿酸潴留。在8小时内观察到类似变化。与单独给予这些利尿剂相比，在慢性舒林酸治疗基础上叠加氢氯噻嗪或吡咯他尼导致利钠作用减弱约30%：萘普生未改变利尿剂的作用。舒林酸预处理未改变氢氯噻嗪或吡咯他尼的尿排泄；萘普生未改变氢氯噻嗪的排泄。基于这些发现，得出结论：NSAIDs发挥直接的肾小管效应，不一定会干扰利尿剂输送至其在肾单位内的作用部位。
