使用合成前列腺素类似物（恩前列素）治疗非甾体抗炎药引起的胃溃疡。

Healing of NSAID-induced gastric ulcers with a synthetic prostaglandin analog (enprostil).

作者信息

Sontag S J, Schnell T G, Budiman-Mak E, Adelman K, Fleischmann R, Cohen S, Roth S H, Ipe D, Schwartz K E

机构信息

Department of Ambulatory Care, Veterans Administration Hospital, Hines, Illinois.

出版信息

Am J Gastroenterol. 1994 Jul;89(7):1014-20.

PMID:8017358

Abstract

OBJECTIVE

Conventional ulcer therapy has not been proven effective in healing gastric ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) if the NSAIDs are continued. Our objective in this study was to determine whether a prostaglandin analog is an effective treatment for such NSAID-induced lesions.

METHODS

To make this determination, we conducted a 9-wk double-blind trial comparing placebo with enprostil 35 micrograms twice daily and three times daily. Use of antacids was not allowed. Three centers entered 145 patients with chronic inflammatory arthritis and osteoarthritis, mean age 63 yr, who required continuous fixed-dose NSAID therapy within the range of therapeutic dosage. The minimum entrance criterion was the presence of either four gastric erosions or one gastric ulcer. Two pretreatment endoscopies within a 2-wk interval were performed to establish the presence of stable baseline gastric lesions. Endoscopy was repeated at wk 6 and 9 during treatment. All groups were similar with regard to age distribution, sex, weight, height, smoking usage, and alcohol consumption.

RESULTS

The ulcer healing rates were 14%, 57%, and 68% at 6 wk and 19%, 68%, and 74% at 9 wk for the groups receiving placebo, enprostil twice daily, and enprostil three times daily, respectively (p < 0.01). Complete mucosal healing of all erosions and ulcers at 9 wk occurred in 59% of enprostil-treated patients and in 10% of placebo-treated patients. Additional gastric erosions and gastric ulcers developed in 16% of placebo patients and 4% of the enprostil patients. Eighteen percent of enprostil patients withdrew early from the study due to adverse experiences, such as diarrhea and abdominal pain.

CONCLUSION

We concluded that during continued NSAID therapy 1) enprostil 35 micrograms (taken either twice daily or three times daily) heals NSAID-induced gastric ulcers and erosions and protects the mucosa from further NSAID-induced gastric injury; 2) gastric ulcers and erosions rarely heal spontaneously, and 3) enprostil results in a high incidence of diarrhea.

摘要

目的

如果继续使用非甾体抗炎药（NSAIDs），传统的溃疡治疗方法尚未被证明对愈合由NSAIDs引起的胃溃疡有效。我们这项研究的目的是确定一种前列腺素类似物是否是治疗此类NSAIDs诱导性损伤的有效方法。

方法

为了做出这一判断，我们进行了一项为期9周的双盲试验，将安慰剂与每天两次、每次35微克恩前列素以及每天三次、每次35微克恩前列素进行比较。不允许使用抗酸剂。三个中心纳入了145例患有慢性炎症性关节炎和骨关节炎的患者，平均年龄63岁，他们需要在治疗剂量范围内持续进行固定剂量的NSAIDs治疗。最低入选标准是存在四处胃糜烂或一处胃溃疡。在2周间隔内进行两次治疗前内镜检查以确定稳定的基线胃部病变的存在。在治疗期间的第6周和第9周重复进行内镜检查。所有组在年龄分布、性别、体重、身高、吸烟习惯和饮酒量方面相似。

结果

接受安慰剂、每天两次恩前列素以及每天三次恩前列素治疗的组在6周时的溃疡愈合率分别为14%、57%和68%，在9周时分别为19%、68%和74%（p<0.01）。在接受恩前列素治疗的患者中，59%在9周时所有糜烂和溃疡实现了完全黏膜愈合，而在接受安慰剂治疗的患者中这一比例为10%。16%的安慰剂组患者出现了额外的胃糜烂和胃溃疡，恩前列素组患者中这一比例为4%。18%的恩前列素组患者因腹泻和腹痛等不良事件提前退出研究。