Jallad N S, Cattan A, Weidler D J
Division of Clinical Pharmacology, University of Miami School of Medicine, FL 33136.
Int J Clin Pharmacol Ther Toxicol. 1993 Aug;31(8):376-81.
Indomethacin, a nonsteroidal anti-inflammatory drug, may cause gastric mucosal damage as shown by fecal blood loss. A randomized, double-blind, placebo-controlled, parallel group study was conducted to determine the effects of 400 mcg b.i.d. misoprostol, a synthetic prostaglandin E1 analog, on intestinal blood loss caused by 50 mg t.i.d. indomethacin. Forty-two arthritic patients, mean age 59 years, received indomethacin for 14 days. Those with baseline blood loss of at least 1.5 ml/day during the first 7 days were randomized to 400 mcg of misoprostol or placebo (days 8 to 14). Fecal blood loss was measured using 51Cr labelled red blood cell technique. Success was defined as a reduction in mean daily blood loss of at least 50% during the treatment period compared to mean daily blood loss during the baseline (pre-treatment) phase. The mean daily blood loss on treatment days 9-15 was not significantly reduced from baseline in either group. These data neither confirm nor deny the effectiveness of misoprostol in reducing fecal blood loss caused by indomethacin. The results may have been confounded by the administration of misoprostol twice daily while indomethacin was administered three times daily. In addition, fecal blood loss as an indicator of gastrointestinal mucosal damage is not a sensitive measure; it is characterized by poor reproducibility and wide fluctuations within individual responses. Inappropriate laboratory techniques may have further reduced the sensitivity and reliability of this procedure.
消炎痛是一种非甾体抗炎药，可导致胃黏膜损伤，表现为粪便失血。本研究进行了一项随机、双盲、安慰剂对照的平行组研究，以确定每日两次服用400微克米索前列醇（一种合成前列腺素E1类似物）对每日三次服用50毫克消炎痛所致肠道失血的影响。42名关节炎患者，平均年龄59岁，接受消炎痛治疗14天。在前7天中基线失血量至少为1.5毫升/天的患者被随机分为服用400微克米索前列醇组或安慰剂组（第8至14天）。使用51Cr标记红细胞技术测量粪便失血量。成功的定义为治疗期间平均每日失血量较基线（治疗前）阶段至少减少50%。在第9至15天的治疗期间，两组的平均每日失血量均未较基线显著减少。这些数据既未证实也未否定米索前列醇在减少消炎痛所致粪便失血方面的有效性。结果可能因米索前列醇每日服用两次而消炎痛每日服用三次而受到混淆。此外，粪便失血作为胃肠道黏膜损伤的指标并非敏感的测量方法；其特点是可重复性差且个体反应波动较大。不恰当的实验室技术可能进一步降低了该方法的敏感性和可靠性。
