An alprostadil analogue and human gastric secretion. A double-blind placebo-controlled study of the effects of a capsule and tablet formulation.
The effects of single oral doses of 800 and 1200 micrograms of the new alprostadil analogue mexiprostil (prostaglandin E1 16-methyl-16-methoxy derivative, MDL 646), presented as tablet and capsule formulation, on basal and pentagastrin-stimulated acid secretion, were studied in 10 healthy volunteers, using a randomized, double-blind, placebo-controlled, 5-way crossover design. Compared to placebo, administration of mexiprostil resulted in a significant inhibition of basal gastric acid secretion, at both doses and formulations. Pentagastrin-stimulated gastric secretion was reduced to a lesser degree and the differences compared to placebo did not achieve statistical significance when adjustments were made for basal effects present before starting stimulation. Total volume of gastric secretion, under basal conditions, was decreased by both doses and formulations, though the changes were significant only at 1200 micrograms for both formulation. The decrease in volume of gastric secretion during pentagastrin infusion did not reach statistical significance. Basal intragastric pH was increased by both doses and formulation, but the changes were significant only for the capsule formulation, at either dose. Neither dose of mexiprostil prevented the decrease in intragastric pH produced by pentagastrin infusion. Tolerability of mexiprostil was excellent with no unwanted effects reported either during or after the study. No changes in heart rate and systemic blood pressure were observed. Laboratory safety parameters were not altered by mexiprostil. There was no significant difference between the effects of both formulations of mexiprostil on any pharmacodynamic parameter.
Müller
P
P
Medizinische Universitätsklinik Heidelberg, Fed. Rep. of Germany.
Dammann
H G
HG
Leucht
U
U
Simon
B
B
D000328:Adult; D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology; D002214:Capsules; D004311:Double-Blind Method; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D010919:Placebos; D011459:Prostaglandins E, Synthetic; D013607:Tablets; D013997:Time Factors
D000897:Anti-Ulcer Agents; D002214:Capsules; D010919:Placebos; D011459:Prostaglandins E, Synthetic; D013607:Tablets; D010418:Pentagastrin; D000527:Alprostadil; C036058:mexiprostil