Geranylgeranylacetone, a Gastromucoprotective Drug, Protects Against NSAID-induced Esophageal, Gastroduodenal and Small Intestinal Mucosal Injury in Healthy Subjects: A Prospective Randomized Study Involving a Comparison with Famotidine

OBJECTIVE: A treatment strategy to inhibit nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal lesions has not yet been established. To clarify whether monotherapy with a gastromucoprotective drug, geranylgeranylacetone (GGA), inhibits NSAID-induced acute mucosal injury of the upper digestive tract and small intestine. METHODS: A prospective, randomized, comparative study. All procedures were performed at Osaka Medical College. The subjects, thirty healthy adult volunteers, were randomly divided into two groups. In the NSAID-GGA group, 75 mg/day of diclofenac sodium and 150 mg/day of GGA were orally administered for two weeks. In the NSAID-FAM group, 75 mg/day of diclofenac sodium and 20 mg/day of famotidine (FAM) were orally administered for two weeks. esophagogastroduodenoscopy (EGD) and video capsule endoscopy (VCE) were performed before and two weeks after drug administration. In addition, we measured fecal occult blood reactions and the fecal calprotectin levels. RESULTS: No significant differences were observed between the groups in the mean increase in esophageal/gastroduodenal lesions. The mean increases in the scores in the NSAID-FAM group (NSAID-GGA group) of small bowel lesions were as follows: erythema: 1.93 ± 0.67 (0.30 ± 0.60), erosions: 1.13 ± 0.54 (0.38 ± 0.35), ulcers: 0.73 ± 0.33 (0.07 ± 0.07) and edema: 0.53 ± 0.44 (0.07 ± 0.07). The scores for erythema and ulcers were significantly lower in the NSAID-GGA group than in the NSAID-FAM group (p=0.032 and 0.0165, respectively). CONCLUSION: We compared the prophylactic effects of a mucoprotective drug, GGA, and an H2RA, famotidine, on mucosal injury involving the esophagus to the small intestine related to the two-week oral administration of diclofenac sodium in healthy volunteers. In the upper digestive tract, the prophylactic effects were similar between the two drugs. However, in the small intestine, GGA more markedly inhibited the development of lesions compared to famotidine.