title: Nonsteroidal anti-inflammatory drug-induced visible and invisible small intestinal injury.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Aichi Medical University School of Medicine, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan.
authors.forename: Yoshitsugi
authors.initials: Y
authors.lastname: Ito
authors.forename: Makoto
authors.initials: M
authors.lastname: Sasaki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Funaki
authors.forename: Naotaka
authors.initials: N
authors.lastname: Ogasawara
authors.forename: Mari
authors.initials: M
authors.lastname: Mizuno
authors.forename: Akihito
authors.initials: A
authors.lastname: Iida
authors.forename: Shinya
authors.initials: S
authors.lastname: Izawa
authors.forename: Ryuta
authors.initials: R
authors.lastname: Masui
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kondo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamura
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Yanamoto
authors.forename: Hisatsugu
authors.initials: H
authors.lastname: Noda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanabe
authors.forename: Noriko
authors.initials: N
authors.lastname: Okaniwa
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Kunio
authors.initials: K
authors.lastname: Kasugai
keywords: diclofenac; healthy subjects; permeability; rebamipide; small intestinal damage