Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury

• Published in: Journal of Clinical Biochemistry and Nutrition Vol. 53; no. 1; pp. 55 - 59
• Main Authors: Ito, Yoshitsugi, Sasaki, Makoto, Funaki, Yasushi, Ogasawara, Naotaka, Mizuno, Mari, Iida, Akihito, Izawa, Shinya, Masui, Ryuta, Kondo, Yoshihiro, Tamura, Yasuhiro, Yanamoto, Kenichiro, Noda, Hisatsugu, Tanabe, Atsushi, Okaniwa, Noriko, Yamaguchi, Yoshiharu, Kasugai, Kunio
• Format: Journal Article
• Language: English
• Published: Japan SOCIETY FOR FREE RADICAL RESEARCH JAPAN 01-07-2013; Japan Science and Technology Agency; the Society for Free Radical Research Japan
• Subjects: diclofenac; healthy subjects; Original; permeability; rebamipide; small intestinal damage; rebamipide; healthy subjects; diclofenac; small intestinal damage; permeability
• ISSN: 0912-0009; 1880-5086
• DOI: 10.3164/jcbn.12-116

Permeation of the small intestinal mucosa is a key mechanism in the induction of enteropathy. We investigated the effect of rebamipide in healthy subjects with diclofenac-induced small intestinal damage and permeability. In this crossover study, each treatment period was 1 week with a 4-week washout period. Diclofenac (75 mg/day) and omeprazole (20 mg/day) plus rebamipide (300 mg/day) or placebo were administered. Capsule endoscopy and a sugar permeability test were performed on days 1 and 7 in each period. Ten healthy subjects were enrolled. Small intestinal injuries were observed on day 7 in 6 of 10 subjects in both groups. Urinary excretion of administered lactulose increased from 0.30% to 0.50% of the initial dose during the first treatment period in the placebo group, and from 0.13% to 0.33% in the rebamipide group. Despite recovery from small-intestinal mucosal damage, the increased permeability in both groups resulted in sustained high levels of lactulose (0.50% to 1.06% in the placebo group and 0.33% to 1.12% in the rebamipide group) through the 4-week washout period. Diclofenac administration induced enteropathy and hyperpermeability of the small intestine. The sustained hyperpermeability during the washout period may indicate the presence of invisible fragility.