yf-476 and Dyspepsia

Hypergastrinaemia induced by proton pump inhibitor (PPI) therapy may cause ECL-cell and parietal-cell hyperplasia and rebound hyperacidity and dyspepsia after PPI withdrawal. The aim of the study was to assess the effect of different dosage-regimens of netazepide, a gastrin/CCK. Six groups of eight healthy subjects participated in a randomised, double-blind study of esomeprazole 40 mg daily for 28 days, in combination with netazepide 1, 5 or 25 mg or placebo, daily, during the last 14 days of esomeprazole or during 14 days after treatment withdrawal. Fasting serum gastrin and plasma CgA were measured during treatment and after withdrawal, as biomarkers of acid suppression and ECL-cell activity, respectively. Dyspepsia was monitored throughout the study.. Esomeprazole increased gastrin and CgA. Netazepide increased gastrin, but not CgA, and inhibited dose dependently the CgA response to esomeprazole. Gastrin and CgA returned to baseline within 2-3 days of esomeprazole withdrawal; netazepide did not shorten that time. There was no rebound dyspepsia after esomeprazole withdrawal.. Esomeprazole and netazepide each increase gastrin, consistent with a secondary effect of gastric acid suppression, but by different mechanisms. Esomeprazole-induced hypergastrinaemia stimulates ECL cells and thereby increases CgA. Netazepide-induced hypergastrinaemia does not increase CgA, because netazepide blocks gastrin/CCK

Topics: Adult; Aged; Anti-Ulcer Agents; Benzodiazepinones; Chromogranin A; Double-Blind Method; Dyspepsia; Esomeprazole; Female; Gastric Acidity Determination; Gastrins; Humans; Male; Middle Aged; Phenylurea Compounds; Proton Pump Inhibitors; Receptor, Cholecystokinin B; Young Adult