ACID-SECRETION DURING INDOMETHACIN THERAPY - EFFECT OF MISOPROSTOL

Secretin is an important physiologic regulator of gastric acid and pan creatic bicarbonate secretion. Endogenous prostaglandins play an impor tant intermediary role, because indomethacin pretreatment prevents the physiological actions of secretin. Misoprostol is a prostaglandin E(1 ) (PGE(1)) analog used for the prevention of nonsteroidal antiinflamma tory drug (NSAID)-induced ulceration. This study sought to determine w hether cotherapy with misoprostol reverses the NSAID-induced blockade of secretin's inhibition of human gastric acid secretion. Seven health y volunteers were studied. Gastric acid secretion was measured during the basal, pentagastin-stimulated and intravenous secretin-inhibited s tates. The studies were then repeated after 3 days of oral indomethaci n (50 mg p.o. t.i.d. for 10 doses) with and without concomitant misopr ostol (200 mu g q.i.d. for 13 doses). Exogenous secretin reduced penta gastrin-stimulated acid secretion by 35%, and this inhibition was redu ced to 9% during indomethacin treatment (p < 0.05). Cotherapy with mis oprostol during indomethacin treatment did not restore secretin's inhi bition of gastric acid secretion; paradoxically, during secretin admin istration, acid secretion increased. When subjects received misoprosto l treatment only, secretin failed to inhibit gastric acid secretion. W e conclude that during indomethacin treatment, cotherapy with misopros tol cannot restore the inhibitory action of secretin to inhibit gastri c acid secretion. These results suggest that PGE(1) is an unlikely int ermediate in secretin's physiological action. Although misoprostol can prevent NSAID-induced ulcers, it does not ameliorate all physiologica l perturbations induced by cyclooxygenase inhibition.