Effects of single daily doses of a pyridil-2-tetrahydrothiophene derivative (40749 RP) on 24 hour H+ activity, nocturnal acid output, gastrin and pepsinogen I profiles in duodenal ulcer patients

Abstract

40749 RP is a pyridil-2-tetrahydrothiophene derivative, belonging to a new class of gastric antisecretory drugs. We compared its effects on gastric secretion with cimetidine. Intragastric acidity, nocturnal acid output, gastrin and pepsinogen-I profiles were measured in patients with duodenal ulcer in clinical remission. A single dose of 100 mg 40749 RP reduced median 24 h gastric acidity as effectively as cimetidine 1000 mg given as four divided doses, 0.63 vs 1.6 mmol/l. Continued treatment with 40749 RP for 10 days reduced the median 24 h gastric acidity even further, to 0.006 mmol/l (p less than 0.001) and significantly increased fasting concentrations of gastrin and pepsinogen-I (p = 0.02). The incremental gastrin secretion to a standard meal was significantly increased after 10 days treatment with 40749 RP when compared with the first day of 40749 RP, or with cimetidine. These results show that 40749 RP exerts a powerful inhibitory effect on gastric acid secretion after a single 100 mg dose, and that this inhibitory effect increases with continued administration.