Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy.
Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Gastroenterology. 2017 Apr;152(5):980-982.e3. doi: 10.1053/j.gastro.2016.12.007. Epub 2016 Dec 19.
The intestinal microbiota might contribute to enteropathy associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs), but there have been few human studies of this association. We performed a placebo-controlled study to determine whether a delayed-release antibiotic formulation (rifaximin-extended intestinal release [EIR]) prevents the development of intestinal lesions in subjects taking daily NSAIDs. Sixty healthy volunteers (median age, 26 y; 42% female) were given the NSAID diclofenac (75 mg twice daily) plus omeprazole (20 mg once daily), and either rifaximin-EIR (400 mg) or placebo, twice daily for 14 days. Subjects were assessed by videocapsule endoscopy at baseline and after 2 weeks of treatment. The primary end point was the proportion of subjects developing at least 1 small-bowel mucosal break at week 2. Secondary end points were the change in the mean number of mucosal lesions and the number of subjects with large erosions and/or ulcers after 14 days of exposure. We detected mucosal breaks in 20% of subjects given rifaximin and in 43% of subjects given placebo (P = .05 in the post hoc sensitivity analysis). None of the subjects in the rifaximin group developed large lesions, compared with 9 subjects in the placebo group (P < .001). Our findings indicate that intestinal bacteria contribute to the development of NSAID-associated enteropathy in human beings. Clinical trial no: EudraCT 2013-000730-36.
肠道微生物群可能与非甾体抗炎药 (NSAIDs) 的使用相关的肠病有关，但对这种相关性的人体研究很少。我们进行了一项安慰剂对照研究，以确定一种延迟释放抗生素制剂（利福昔明延长肠释放[EIR]）是否可以预防接受每日 NSAIDs 治疗的患者出现肠道损伤。60 名健康志愿者（中位数年龄 26 岁；42%为女性）接受 NSAID 双氯芬酸（每日 2 次，每次 75mg）加奥美拉唑（每日 1 次，每次 20mg），以及利福昔明-EIR（400mg）或安慰剂，每日 2 次，共 14 天。在基线和治疗 2 周后，通过视频胶囊内镜对受试者进行评估。主要终点是在第 2 周时至少有 1 名小肠道黏膜破裂的受试者比例。次要终点是治疗 14 天后黏膜病变的平均数量变化以及有大的糜烂和/或溃疡的受试者数量。给予利福昔明的受试者中有 20%出现黏膜破裂，而给予安慰剂的受试者中有 43%出现黏膜破裂（事后敏感性分析中 P =.05）。与安慰剂组的 9 名受试者相比，利福昔明组没有受试者出现大的病变（P <.001）。我们的研究结果表明，肠道细菌有助于人类 NSAID 相关肠病的发生。临床试验编号：EudraCT 2013-000730-36。
