Trimoprostil plasma concentration-gastric acid inhibition relationships in duodenal ulcer patients.
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.
D000328:Adult; D000368:Aged; D000897:Anti-Ulcer Agents / Q000097:blood* / Q000494:pharmacology; D003864:Depression, Chemical; D015232:Dinoprostone / Q000031:analogs & derivatives*; D004381:Duodenal Ulcer / Q000378:metabolism / Q000503:physiopathology*; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011459:Prostaglandins E, Synthetic / Q000097:blood* / Q000494:pharmacology; D013997:Time Factors
D000897:Anti-Ulcer Agents; D011459:Prostaglandins E, Synthetic; C038879:trimoprostil; D015232:Dinoprostone