Therapeutic Effects of Rebamipide in Patients with Gastric Ulcer

Park, Soo Heon; Jung, Woon Tae; Suh, Jung Han; Chung, Myung Hee; Chung, In Sik; Lee, Yong Chan; Park, In Suh; Song, Guen Am; Yang, Ung Suk; Rew, Jong Sun; Yoon, Chong Mann; Choi, Kyoo Wan

Abstract

BACKGROUND/AIMS: Helicobacter pylori has been shown to be an important pathogen of gastric disorder including gastritis and gastric ulcer. One of the potential toxic factors involving gastric mucosal cell injury is reactive oxidants, which are released from activated neutrophils. Rebamipide had been reported to promote mucus synthesis, mucosal prostaglandin content, and rapid ulcer healing, It has recently been reported to inhibit the production of oxygen derived free radicals from stimulated neutrophils. We conducted this study to evaluate the effects of rebamipide on gastric ulcer healing and reactive oxygen metabolite production.
METHODS
In this multicenter study conducted in Korea, combination treatment of rebamipide and ranitidine was compared with ranitidine alone in 108 patients with gastric ulcer patients. Pre- and post-treatment endoscopic findings and concentration of reactive oxygen metabolite produced were used to evaluate efficacy. The efficacy of rebamipide and ranitidine versus ranitidine was evaluated using endoscopy results, and tissue lipid peroxides by thiobarbituric acid and myeloperoxide concentration.
RESULTS
The percentage of ulcer size reduction was significantly higher with rebamipide and ranitidine group than with placebo and ranitidine group(size reduction: 71.5% vs 58.3% P=0.04556). The myeloperoxidase activities at ulcer margin in rebamipide and ranitidine group patients were 96.7+/-13.4 unit/mg protein in baseline and 53.8+9.9 unit/mg protein in follow up (P=0.0065). The myeloperoxidase activities at ulcer margin in placebo and ranitidine group patients were 90.2+9.1 unit/mg protein in baseline and 63.1+6.7 unit/mg protein in follow up (P=0.0668). The thiobarbituric acid activities at ulcer margin in rebamipide and ranitidine group patients were 34.7+5.3 nmol of MDA/mg protein in baseline and 24.1W3.1 nmol of MDA/mg protein in follow up. The thiobarbituric acid activities at ulcer margin in placebo and ranitidine group patients were 14.8+1.5 nmol of MDA/mg protein in baseline and 24.3+2.7 nmol of MDA/mg protein in follow up (P=0.0059). The thiobarbituric acid activities at ulcer margin in H. pylori positive and negative patients were 28.1+2.1 nmol of MDA/mg protein and 25.3+4.7 nmol of MDA/mg protein, respectively. The myeloperoxidase activities at ulcer margin in H. pylori positive and negative patients were 79.9+5.3 unit/mg protein and 40.4+25.3 unit/mg protein, respectively (P=0.0001). The cumulative relapse rate was examined starting at 24 week after ulcer treatment. The rate was lower in rebamipide and ranitidine group patients, but insignificantly(19.2% vs 27.3%, P=0.0857).
CONCLUSIONS
These results suggest that rebamipide promote gastric ulcer healing by decreasing reactive oxygen metabolite production in patients with gastric ulcer.