Trimoprostil plasma concentration--gastric acid inhibition relationships: potentiation by food.
A single, oral, 1.5-mg dose of trimoprostil was taken before a standard meal and a matching placebo was taken after a standard meal by 10 subjects (group A). A second group of 10 subjects took placebo before a meal and trimoprostil after the meal (group B), while a third group took placebo both before and after the standard meal (group C). Food-stimulated gastric acid production was measured by intragastric titration for 6.5 hr after dosing. Trimoprostil taken after the meal had a greater effect on gastric acid secretion than when taken before the meal: Duration of effect was 5 to 5.5 hr in group B and 2 to 2.5 hr in group A. Blood samples were drawn and assayed for trimoprostil by gas chromatography-mass spectrometry. Mean trimoprostil plasma concentration and mean inhibition of gastric acid secretion data were fit to two models by the Hill equation. The mean plasma concentration associated with 50% inhibition of gastric acid secretion was 1.25 ng/ml. Trimoprostil plasma concentrations between 3 and 4 ng/ml were associated with 70% to 80% gastric acid inhibition. Overall, there appears to be a pharmacokinetic-pharmacologic correlation between trimoprostil plasma concentrations and inhibition of gastric acid secretion. Trimoprostil (1.5 mg) in the presence of food appears to have a therapeutic advantage, in that it decreases acid secretion longer than when taken without food and suffers no loss of bioavailability.
D000328:Adult; D000897:Anti-Ulcer Agents / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D001682:Biological Availability; D015232:Dinoprostone / Q000031:analogs & derivatives*; D004311:Double-Blind Method; D004435:Eating; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D011897:Random Allocation; D013997:Time Factors
D000897:Anti-Ulcer Agents; D011459:Prostaglandins E, Synthetic; C038879:trimoprostil; D015232:Dinoprostone