Acid secretory capacity and plasma gastrin concentration after administration of omeprazole to normal subjects

Abstract

SUMMARY In a randomized double‐blind study, two groups of eight healthy volunteers received either placebo or omeprazole 40 mg o.m. for 14 days. Fasting plasma gastrin concentration and peak acid output in response to a maximal intravenous dose of pentagastrin were measured before, during and after the 14 days of treatment. Omeprazole caused a 68% (mean) decrease in the peak acid output when measured 24 hours after the last dose, with a simultaneous increase in the fasting plasma gastrin concentration. When measured 1, 2, 3 and 8 weeks after cessation of treatment, there was no significant difference in the peak acid output between the two groups. The study demonstrates that there is no increase in the acid production capacity after 2 weeks of treatment with omeprazole. Thus it would appear that the rise in the plasma gastrin concentration during short‐term treatment with omeprazole does not induce parietal cell hypertrophy or hyperplasia.

Effects of Dexlansoprazole MR, a Novel Dual Delayed Release Formulation of a Proton Pump Inhibitor, on Plasma Gastrin Levels in Healthy Subjects

“…Differences in integrated mean gastrin levels between the lansoprazole and placebo groups were significant on days 14, 16, and 18 but were not significant thereafter. Several studies have shown that although gastrin levels initially increase in response to treatment with PPIs, they plateau after several months of therapy 8,17,22,32,39,40 Other studies have shown that mean gastrin levels return to near‐baseline levels approximately 1 week after PPI therapy is discontinued, as was observed in the present study with dexlansoprazole MR 2 , 20 , 21 , 26 …”

“…Several studies have shown that although gastrin levels initially increase in response to treatment with PPIs, they plateau after several months of therapy. 8,17,22,32,39,40 Other studies have shown that mean gastrin levels return to near-baseline levels approximately 1 week after PPI therapy is discontinued, as was observed in the present study with dexlansoprazole MR. 2,20,21,26 There was a large variance in plasma gastrin AUC 24 values both at baseline and during the 3 dosing periods, which was predominantly attributable to a small number of subjects with gastrin levels that were higher at baseline than the values observed in the majority of the subjects in the study. Several of these subjects experienced moderately high gastrin levels that were 400 pg/mL or greater and/or AUC 24 values 8000 pg⋅h/ mL or greater during 1 or more of the 3 dosing periods.…”

“…On this basis, theoretical concerns have been raised regarding elevated gastrin levels in patients receiving long‐term treatment with PPIs. The inhibition of gastric acid secretion by PPIs generally leads to modest increases in plasma gastrin levels, 17 – 25 and gastrin levels return to baseline shortly after PPI therapy is discontinued 2 , 20 , 21 , 26 . In a few early long‐term studies of omeprazole, it was observed that hypergastrinemia was accompanied by evidence of hyperplasia of the ECL cells 27 , 28 .…”

“…The inhibition of gastric acid secretion by PPIs generally leads to modest increases in plasma gastrin levels, [17][18][19][20][21][22][23][24][25] and gastrin levels return to baseline shortly after PPI therapy is discontinued. 2,20,21,26 In a few early long-term studies of omeprazole, it was observed that hypergastrinemia was accompanied by evidence of hyperplasia of the ECL cells. 27,28 Despite these early concerns, no evidence of gastric cell dysplasia, neoplasia, or carcinoid formation attributable to elevated gastrin levels has been demonstrated in long-term PPI users.…”

Systematic review: rebound acid hypersecretion after therapy with proton pump inhibitors

“…All studies investigated oral PPI administration. Four studies had a double‐blind randomized‐clinical design, 5, 17–19 the other four trials had an open label design 20–23 . Gastric acid production was measured with different methods and techniques.…”