Acid secretion during indomethacin therapy. Effect of misoprostol.
Secretin is an important physiologic regulator of gastric acid and pancreatic bicarbonate secretion. Endogenous prostaglandins play an important intermediary role, because indomethacin pretreatment prevents the physiological actions of secretin. Misoprostol is a prostaglandin E1 (PGE1) analog used for the prevention of nonsteroidal antiinflammatory drug (NSAID)-induced ulceration. This study sought to determine whether cotherapy with misoprostol reverses the NSAID-induced blockade of secretin's inhibition of human gastric acid secretion. Seven healthy volunteers were studied. Gastric acid secretion was measured during the basal, pentagastin-stimulated and intravenous secretin--inhibited states. The studies were then repeated after 3 days of oral indomethacin (50 mg p.o. t.i.d. for 10 doses) with and without concomitant misoprostol (200 micrograms q.i.d. for 13 doses). Exogenous secretin reduced pentagastrin-stimulated acid secretion by 35%, and this inhibition was reduced to 9% during indomethacin treatment (p < 0.05). Cotherapy with misoprostol during indomethacin treatment did not restore secretin's inhibition of gastric acid secretion; paradoxically, during secretin administration, acid secretion increased. When subjects received misoprostol treatment only, secretin failed to inhibit gastric acid secretion. We conclude that during indomethacin treatment, cotherapy with misoprostol cannot restore the inhibitory action of secretin to inhibit gastric acid secretion. These results suggest that PGE1 is an unlikely intermediate in secretin's physiological action. Although misoprostol can prevent NSAID-induced ulcers, it does not ameliorate all physiological perturbations induced by cyclooxygenase inhibition.
Taylor
S D
SD
Division of Gastroenterology, University of Michigan, Ann Arbor, USA.
Chey
W Y
WY
Scheiman
J M
JM
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D016595:Misoprostol / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D012633:Secretin / Q000037:antagonists & inhibitors / Q000502:physiology*
D016595:Misoprostol; D012633:Secretin; D010418:Pentagastrin; D007213:Indomethacin