薬理と治療

Abstract

Objectives Pirfenidone（Pirespa）, clinically used to treat idiopathic pulmonary fibrosis, often has the side effects of gastrointestinal disorders, including abdominal discomfort and anorexia. The purpose of this study was to assess the ameliorative effect of gastrointestinal prokinetic agents（mosapride or rikkunshi－to）on the pirfenidone－induced suppression of gastrointestinal motility in rats. Methods A test meal including 0.25％（w／v）Evans blue was orally administered at 1 hr after pirfenidone treatment with／without mosapride or rikkunshi－to. Animals were euthanized at 15 min after administration of the test meal, and the stomach and small intestine were isolated. Gastric emptying was measured using a spectrophotometer. Small intestinal transit was measured by calculating the distance the dye traveled to the total length of the small intestine. Results Pirfenidone at doses of 30 mg／kg or above induced a significant decrease in the gastric emptying rate, and 100 and 300 mg／kg of pirfenidone decreased the small intestinal transport rate. Concomitant dosing with mosapride at 3 and 10 mg／kg led to significant amelioration of the decrease in the gastric emptying rate induced by 100 mg／kg of pirfenidone. Mosapride at 1 mg／kg or above ameliorated the decreased small intestinal transport rate. Rikkunshi－to also showed ameliorating effects on the decrease in gastric emptying rate at 500 mg／kg and in the small intestinal transport rate at 100 mg／kg or above. Conclusion These results indicated that mosapride and rikkunshi－to are useful demulcents for treatment of gastrointestinal disorders induced by pirfenidone.