lafutidine and Chronic-Disease

We conducted a retrospective cohort study evaluating the efficacy and usefulness of the addition of lafutidine, a novel histamine H2-receptor antagonist, in treatment of patients with idiopathic chronic urticaria whose disease was not well controlled with histamine H1-receptor antagonists. Based on the assessment of global improvement, moderate or better improvement was achieved in 39 of 46 patients (85%) after 1-3 weeks of additional administration of lafutidine and 35 patients (76%) after 3 months. No incidence of drug-related adverse reactions was reported in any patient. Lafutidine was rated as useful or better in 34 patients (74%) after 3 months of treatment. The usefulness of the drug was not affected by differences in background factors, such as disease duration, previous treatment duration and the number of concomitant H1-receptor antagonists. Lafutidine appears to be a promising addition to histamine H1-receptor antagonist therapy for the treatment of chronic urticaria resistant to treatment with H1-receptor antagonists alone.

Topics: Acetamides; Adolescent; Adult; Aged; Chronic Disease; Drug Therapy, Combination; Female; Histamine H1 Antagonists; Histamine H2 Antagonists; Humans; Male; Middle Aged; Piperidines; Pyridines; Retrospective Studies; Urticaria; Young Adult

Oral administration of an ammonia solution (0.01%) or a sodium taurocholate solution (TCA solution, 5 mM) as drinking water for 4 weeks or 13 weeks, respectively, resulted in gastric mucosal thinning and decreased parietal cell numbers. Oral administration of TCA solution also caused cell infiltration in the lamina propria of the mucosa and mucosal fibrosis. When lafutidine (3, 10 mg/kg) was administered orally once daily for one week after the withdrawal of ammonia or TCA solution, the recovery of the mucosal thickness in the fundic gland area and the parietal cell number were significantly accelerated, and the recovery of mucosal thickness in the pyloric gland area also tended to be accelerated. Lafutidine at 10 mg/kg for 1 week had no influence on normal mucosal thickness and parietal cell numbers. At the doses that produce equal or greater acid antisecretory effect than lafutidine, oral administration of cimetidine (30 mg/kg) and famotidine (1 mg/kg) had no effect on either of these atrophy indexes. These results demonstrate that lafutidine, unlike cimetidine and famotidine, can accelerate the healing of mucosal injuries in ammonia- and TCA-induced chronic gastritis models.

Topics: Acetamides; Ammonia; Animals; Anti-Ulcer Agents; Cell Count; Chronic Disease; Cimetidine; Famotidine; Gastric Mucosa; Gastritis; Humans; Male; Parietal Cells, Gastric; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Taurocholic Acid

We examined the anti-ulcer effects of FRG-8813, a new-type histamine H2-receptor antagonist, in chronic ulcer models of rats and mice (W/WV). FRG-8813, given orally twice a day for 7 days, accelerated the healing of gastric or duodenal ulcer induced by acetic acid injection or application at the non-antisecretory doses (0.3 approximately 3 mg/kg). Administration of FRG-8813 to rats with ulcers increased the amounts of mucus in the gastric mucosa. These actions of FRG-8813 were more potent than those of famotidine or cimetidine. In W/WV mice, several ulcers spontaneously developed on gastric mucosa during the 8 weeks after the birth. The ulcers were aggravated by several unknown factors after the ulcer generation in W/WV mice. The aggravation of ulcers was inhibited by the 4-week administration of FRG-8813 with diet at the dose of 1 or 10 mg/kg/day, but was not inhibited by cimetidine at the dose of 100 mg/kg/day. From these results, we suggest that FRG-8813 is able to accelerate the healing of ulcers by antisecretory plus increasing actions on the integrity of the gastric mucosal defense mechanisms; therefore FRG-8813 is expected to be a useful drug for the treatment of gastric or duodenal ulcers in humans.

Topics: Acetamides; Animals; Chronic Disease; Disease Models, Animal; Duodenal Ulcer; Gastric Acid; Histamine H2 Antagonists; Male; Mice; Piperidines; Pyridines; Rats; Rats, Wistar; Stomach Ulcer