Rebamipide Mechanism of Action in Peptic Ulcer Disease
Primary Mechanisms of Action
Rebamipide works through multiple complementary mechanisms that enhance mucosal protection and accelerate ulcer healing, fundamentally different from acid-suppressive therapies. The drug stimulates endogenous prostaglandin generation in gastric mucosa, increases mucus glycoprotein synthesis, and promotes epithelial cell migration and proliferation at ulcer sites 1, 2.
Mucosal Protection Mechanisms
Prostaglandin stimulation is a cornerstone mechanism, with rebamipide increasing endogenous prostaglandin production in gastric mucosa, which enhances mucosal blood flow and bicarbonate secretion 1, 3.
Mucus enhancement occurs through increased synthesis of gastric mucus glycoprotein components, strengthening the protective mucus barrier 1, 3.
Growth factor activation is achieved by upregulating epidermal growth factor (EGF) and its receptor (EGF-R) expression in both normal and ulcerated gastric mucosa, promoting epithelial cell proliferation and re-epithelialization 1, 4.
Anti-Inflammatory and Antioxidant Actions
Reactive oxygen species (ROS) scavenging protects gastric mucosa from oxidative damage caused by various ulcerogenic factors 1, 3.
Neutrophil inhibition reduces inflammatory cell activation and infiltration at sites of mucosal injury 1, 3.
Cytokine modulation attenuates production of inflammatory cytokines and chemokines, particularly those stimulated by NSAIDs and H. pylori infection 1, 3.
COX-2 pathway effects include modulation of cyclooxygenase-2 expression and prostaglandin E receptor activity 3.
Clinical Efficacy in Specific Ulcer Etiologies
NSAID-Related Ulcers
Rebamipide demonstrates particular effectiveness in NSAID-induced gastric ulcers, with complete healing achieved in most patients and significant improvement in gastric inflammation scores (2.38 vs. 1.75, p=0.011). 5 The drug counteracts NSAID-induced mucosal damage by restoring prostaglandin synthesis that NSAIDs suppress and by reducing NSAID-stimulated inflammatory responses 1, 5.
H. pylori-Associated Ulcers
Rebamipide attenuates immunoinflammatory responses in H. pylori-infected gastric mucosa, potentially preventing progression from gastritis to peptic ulcer disease 1, 2.
The drug may enhance H. pylori eradication rates when added to standard eradication regimens, though this requires further validation 1, 2.
Post-eradication therapy with rebamipide may accelerate mucosal normalization and healing 2.
Standard Adult Dosing Regimen
The established dosing is rebamipide 100 mg three times daily for 8 weeks, which produces significant symptom improvement (symptom scores: 5.9 vs. 0.6, p<0.001) and promotes complete ulcer healing with minimal adverse effects. 5
Treatment Duration Considerations
Eight-week courses are standard for gastric ulcer healing, with assessment at 4 weeks for symptom improvement and adverse effects 5.
Extended therapy may be considered for patients with ongoing NSAID use or persistent H. pylori infection requiring suppression of gastro-intestinal inflammation 2.
Quality of Ulcer Healing
A critical advantage of rebamipide over antisecretory drugs is improvement in the quality of ulcer healing, not just healing speed. The drug promotes better scar formation and reduces future ulcer recurrence rates through enhanced epithelial regeneration and gland reconstruction 1, 4.
EGF and EGF-R upregulation in regenerating glands of the ulcer scar contributes to superior tissue repair 4.
Accelerated re-epithelialization and improved mucosal architecture reduce vulnerability to recurrent injury 1, 4.
Important Clinical Caveats
Rebamipide is not mentioned in major Western guidelines (WSES, AGA, ACG) for peptic ulcer disease management, as it remains primarily used in Asian countries, particularly Japan where it was developed and approved 6.
Combination with standard therapies may be beneficial—rebamipide's mechanisms complement rather than replace acid suppression with PPIs and H. pylori eradication 1, 2.
Safety profile is favorable with few adverse effects reported in clinical use, making it well-tolerated for extended courses 5.
Potential applications beyond ulcer healing include prevention of preneoplastic lesions and management of inflammatory bowel disease, though these require further rigorous clinical trials 2, 3.