Wong F, Massie D, Hsu P, Dudley F
Department of Gastroenterology, Alfred Hospital, Prahran, Victoria, Australia.
J Hepatol. 1995 Jul;23(1):1-7. doi: 10.1016/0168-8278(95)80303-3.
BACKGROUND/AIMS: Indomethacin has been shown to have adverse effects on renal function in patients with well-compensated alcoholic cirrhosis. The aim of this study was to determine whether an oral prostaglandin E1 analogue, misoprostol, could prevent this indomethacin-induced renal dysfunction.
Six patients with well-compensated alcoholic cirrhosis were studied. Renal hemodynamics and tubular function were assessed by clearance techniques before and after an oral dose of (i) 50 mg of indomethacin alone (I50), and (ii) a combination of I50 and 200 micrograms of misoprostol.
I50 produced a significant reduction in glomerular filtration rate, a fall in effective renal plasma flow and an increase in renal vascular resistance. Two hundred micrograms of misoprostol was able to abolish the deleterious renal effects of indomethacin totally, yielding an increase in glomerular filtration rate and effective renal plasma flow and a decrease in renal vascular resistance as well as an increase in urinary volume and urinary sodium excretion. These beneficial effects were maximal in the hour immediately following medication, but were only transient, and this may be a limiting factor in its clinical use.
If the beneficial renal effects of misoprostol could be confirmed after chronic administration, then the vasodilatory, natriuretic and diuretic potential of 200 micrograms of misoprostol could be of potential therapeutic value in patients with well-compensated alcoholic cirrhosis who require non-steroidal anti-inflammatory drug therapy.
背景/目的:已表明吲哚美辛对代偿良好的酒精性肝硬化患者的肾功能有不良影响。本研究的目的是确定口服前列腺素E1类似物米索前列醇是否能预防吲哚美辛诱导的肾功能障碍。
对6例代偿良好的酒精性肝硬化患者进行研究。在口服以下药物前后,通过清除技术评估肾脏血流动力学和肾小管功能:(i)单独服用50mg吲哚美辛(I50),以及(ii)I50与200μg米索前列醇联合使用。
I50导致肾小球滤过率显著降低、有效肾血浆流量下降和肾血管阻力增加。200μg米索前列醇能够完全消除吲哚美辛对肾脏的有害影响,使肾小球滤过率和有效肾血浆流量增加,肾血管阻力降低,同时尿量和尿钠排泄增加。这些有益作用在用药后的即刻一小时内最大,但只是短暂的,这可能是其临床应用的一个限制因素。
如果米索前列醇在长期给药后对肾脏的有益作用能够得到证实,那么200μg米索前列醇的血管舒张、利钠和利尿潜力对于需要非甾体抗炎药治疗的代偿良好的酒精性肝硬化患者可能具有潜在的治疗价值。