trimoprostil and Duodenal-Ulcer

Trimoprostil is a new synthetic prostaglandin E2 analogue that inhibits acid secretion and has mucosal protective properties. It was compared with cimetidine to assess its effectiveness in the short-term treatment of duodenal ulcer. Seven centres recruited 107 patients, who were randomized to receive either 3 mg trimoprostil daily (n = 54) or 1 g cimetidine daily (n = 53) for 4 weeks, the drugs being taken in four divided doses. Of patients completing treatment, 23 of 40 (58%) healed with trimoprostil, compared with 47 of 53 (89%) with cimetidine (p less than 0.001). Both drugs relieved daytime and nighttime pain, but cimetidine was significantly quicker. Eight patients taking trimoprostil were withdrawn because of pain, nausea, and vomiting, but none taking cimetidine; diarrhoea did not occur with trimoprostil. There were no clinically significant changes in haematology or in biochemistry studies. In conclusion, trimoprostil was not as effective as cimetidine in the treatment of duodenal ulcer.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Cimetidine; Clinical Trials as Topic; Dinoprostone; Duodenal Ulcer; Female; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation

120 adult outpatients with endoscopically proven duodenal ulcer were randomly allocated to three groups of 40, treated in a double-blind manner with cimetidine 400 mg twice daily, trimoprostil 3 mg twice daily and trimoprostil 3 mg at bedtime. Trimoprostil was administered as a slow release formulation. Healing rates after 4 weeks were 78, 74 and 58%, respectively, the difference being not significant (p = 0.12). Similarly there was no significant difference regarding subjective symptoms, side effects and biochemical analysis. Healed patients were followed at bimonthly intervals for 6 months. The relapse rates were 71, 59 and 61% for patients initially treated with cimetidine, trimoprostil 6 or 3 mg, respectively, a difference not statistically significant.

Topics: Adolescent; Adult; Aged; Anti-Ulcer Agents; Cimetidine; Delayed-Action Preparations; Dinoprostone; Double-Blind Method; Duodenal Ulcer; Female; Follow-Up Studies; Humans; Male; Middle Aged; Random Allocation

The effect of varying oral doses of 11R, 16, 16-trimethyl prostaglandin E2 (TmPGE2) on meal-stimulated gastric acid secretion and serum gastrin concentrations was studied in 10 male subjects with asymptomatic duodenal ulcer disease. A liquid protein meal was infused intragastrically 0.5 h and 3.5 h after drug administration. TmPGE2 inhibited gastric acid secretion in a dose dependent manner during the first meal and no significant effect was observed during the second meal. Except for the highest dose, no TmPGE2 was detected in plasma 3 h after drug administration. The degree of inhibition of meal-stimulated gastric acid was positively correlated with the plasma level of TmPGE2, but it was not due to inhibition of postprandial gastrin release. The results indicate that oral TmPGE2 inhibits meal-stimulated gastric acid secretion but not gastrin release in humans with asymptomatic duodenal ulcer disease.

Topics: Adult; Aged; Analysis of Variance; Dinoprostone; Duodenal Ulcer; Food; Gastric Acid; Gastric Mucosa; Gastrins; Humans; Male; Middle Aged; Prostaglandins E, Synthetic; Random Allocation

The effect of single 0.25 mg, 0.75 mg, 1.5 mg, and 3.0-mg oral doses of trimoprostil and placebo on the inhibition of meal-stimulated gastric acid secretion was investigated in duodenal ulcer patients. Drug and placebo were administered in a double-blind, randomized, crossover study under fasting conditions. A bactopeptone meal was administered 30 minutes after dosing. Gastric acid output was measured by intragastric titation (pH 5.5) and trimoprostil plasma concentrations were measured by a specific gas chromatography-negative chemical ionization-mass spectrometric method. Meal-stimulated gastric acid secretion was significantly reduced when compared to placebo for one hour after 0.25 mg, 1.5 hours after 0.75 mg, and for 2.5-3.0 hours after both 1.5 mg and 3.0 mg doses. The maximal inhibition of gastric acid ranged from 65% reduction after 0.75 mg to 74% after 1.5 mg to 82% after 3.0-mg doses. Trimoprostil was rapidly absorbed and eliminated; terminal elimination half-life ranged from 21 to 45 minutes. Both maximum concentration and area under the plasma concentration-time curve increased proportionately with an increase in the dose. The concentration-effect data at a given dose were simultaneously fit to a pharmacokinetic/pharmacologic effect model. An IC50 (plasma concentration needed to elicit a 50% inhibition effect) value of 0.2 ng/mL was observed at doses of 0.75 mg to 3.0 mg. Overall, trimoprostil was effective in inhibiting acid output in a dose-related manner in duodenal ulcer patients.

Topics: Adult; Aged; Anti-Ulcer Agents; Depression, Chemical; Dinoprostone; Duodenal Ulcer; Gastric Acid; Humans; Kinetics; Male; Middle Aged; Models, Biological; Prostaglandins E, Synthetic; Time Factors