Weir M R, Klassen D K, Hall P S, Schubert C, Voss T E, Stromatt S C, Brown J A
Department of Medicine, University of Maryland Hospital, Baltimore 21201.
J Clin Pharmacol. 1991 Aug;31(8):729-35. doi: 10.1002/j.1552-4604.1991.tb03768.x.
A prospective, randomized, open-label, triple crossover comparison of the effects of indomethacin, misoprostol, or the combination, on renal function was performed to assess the ability of an oral prostaglandin E analogue, misoprostol, to minimize indomethacin-induced decline in renal function in middle-aged women. Twelve healthy women (mean age: 60.5 +/- 1.6 yr) with normal renal function (serum creatinine: 81 +/- 9 umol/L) were studied; six women were normotensive, and six women were hypertensive with their blood pressure controlled with 50-mg hydrochlorothiazide daily. All patients were placed on a 2-g sodium daily diet for 2 weeks before initiation of the study. The subjects were prospectively randomized to receive each of three 4-day treatments of indomethacin (25 mg q 6hr), misoprostol (200 mcg q 6hr), or the combination of drugs with a 4-day washout between each treatment period. Measurements of GFR (urine accumulation of 99mTc-DTPA) and RPF (serum disappearance 131I-Hippuran), and urine collections for electrolytes were obtained before the first treatment period and on the fourth day of each treatment period. Three of the six hypertensive patients and three of the six normotensive patients had a decrease (greater than 10%) in GFR associated with indomethacin therapy. When misoprostol was given with the indomethacin, four of these six patients did not experience a decline in GFR (baseline GFR for six patients: 75.4 +/- 6.6 mL/min/1.73m2, GFR after indomethacin: 57.8 +/- 9.5 mL/min/1.73m2, GFR with combination of indomethacin and misoprostol: 69.7 +/- 3.5 mL/min/1.73m2. RPF was not consistently altered by subacute/chronic dosing of indomethacin, misoprostol, or the combination of the drugs. The authors conclude that misoprostol ameliorates indomethacin-induced renal dysfunction in salt-restricted and diuretic-treated middle-aged women with normal serum creatinine.
进行了一项前瞻性、随机、开放标签的三联交叉比较研究，以评估吲哚美辛、米索前列醇或二者联合使用对肾功能的影响，目的是评估口服前列腺素E类似物米索前列醇能否将吲哚美辛引起的中年女性肾功能下降降至最低。研究对象为12名肾功能正常（血清肌酐：81±9μmol/L）的健康女性（平均年龄：60.5±1.6岁）；其中6名女性血压正常，6名女性患有高血压，通过每日服用50mg氢氯噻嗪控制血压。在研究开始前，所有患者接受为期2周的每日2g钠饮食。研究对象被前瞻性随机分组，接受三种为期4天的治疗，分别为吲哚美辛（25mg，每6小时一次）、米索前列醇（200μg，每6小时一次）或二者联合用药，每个治疗周期之间有4天的洗脱期。在第一个治疗周期前以及每个治疗周期的第四天，测量肾小球滤过率（99mTc-DTPA尿液蓄积量）、肾血浆流量（131I-马尿酸血清消失率），并收集尿液检测电解质。6名高血压患者中有3名以及6名血压正常患者中有3名在接受吲哚美辛治疗时肾小球滤过率下降（超过10%）。当米索前列醇与吲哚美辛联合使用时，这6名患者中有4名肾小球滤过率未下降（6名患者的基线肾小球滤过率：75.4±6.6mL/min/1.73m2，吲哚美辛治疗后肾小球滤过率：57.8±9.5mL/min/1.73m2，吲哚美辛与米索前列醇联合使用时肾小球滤过率：69.7±3.5mL/min/1.73m2）。亚急性/慢性给予吲哚美辛、米索前列醇或二者联合用药，肾血浆流量未出现一致变化。作者得出结论，米索前列醇可改善血清肌酐正常、接受限盐和利尿剂治疗的中年女性因吲哚美辛引起的肾功能不全。
