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A placebo-controlled study to assess the effects of 7-day dosing with 10, 20 and 40 mg rabeprazole on 24-h intragastric acidity and plasma gastrin in healthy male subjects

Williams, MP; Blanshard, C; Millson, C; Sercombe, J; Pounder, RE; (2000) A placebo-controlled study to assess the effects of 7-day dosing with 10, 20 and 40 mg rabeprazole on 24-h intragastric acidity and plasma gastrin in healthy male subjects. Alimentary Pharmacology and Therapeutics , 14 (6) 691 - 699.

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Abstract

AIM: To compare the effects of rabeprazole 10, 20 and 40 mg o.d. on 24- h intragastric acidity and plasma gastrin concentration in a randomized, double-blind placebo-controlled trial. METHODS: Twenty-four healthy male volunteers were studied on the 7th day of morning dosing with either placebo or rabeprazole 10, 20 or 40 mg in a crossover fashion. On day 7, hourly intragastric acidity was measured for 24 h from 08.00 hours by gastric aspiration. Plasma gastrin concentrations were also measured hourly from 08.00 to 24.00 hours, and 2-hourly thereafter. RESULTS: Compared with placebo, rabeprazole 10, 20 and 40 mg produced significant dose-related decreases in intragastric acidity (median 24-h integrated acidity=697, 186, 129 and 82 mmol h/L, respectively). This was associated with significant elevation of plasma gastrin concentration (median 24-h integrated gastrin=141, 1184, 1484 and 1763 pmol.h/L, respectively). Rabeprazole 40 mg resulted in significantly decreased acidity compared with both 10 and 20 mg, and in longer times for which intragastric pH was maintained at > 3 (19. 2 h vs. 17.3 h and 17.5 h) and > 4 (17 h vs. 14.2 h and 15.2 h), but was accompanied by significantly increased plasma gastrin. There was a consistent trend for greater antisecretory activity for 20 mg compared with 10 mg, but these differences did not reach statistical significance. The interindividual variability in antisecretory response was greatest with 10 mg. CONCLUSIONS: Rabeprazole 10, 20 and 40 mg produce significant, profound dose-related inhibition of gastric acid secretion. Taking into account reciprocal increases in plasma gastrin and the interindividual variation in antisecretory response, 20 mg appears to be the preferred dose for routine clinical use

Type:Article
Title:A placebo-controlled study to assess the effects of 7-day dosing with 10, 20 and 40 mg rabeprazole on 24-h intragastric acidity and plasma gastrin in healthy male subjects
Additional information:UI - 20307243 LA - eng RN - 0 (Anti-Ulcer Agents) RN - 0 (Benzimidazoles) RN - 0 (Gastrins) RN - 117976-90-6 (E 3810) PT - Clinical Trial PT - Journal Article PT - Randomized Controlled Trial DA - 20000801 IS - 0269-2813 SB - IM CY - ENGLAND JC - A5D
Keywords:0 (Anti-Ulcer Agents), 0 (Benzimidazoles), 0 (Gastrins), 117976-90-6 (E 3810), ACID, administration & dosage, adult, Anti-Ulcer Agents, Benzimidazoles, Blood, clinical, Clinical trial, CONTROLLED TRIAL, Cross-Over Studies, difference, DOUBLE BLIND, DOUBLE-BLIND, Double-Blind Method, drug effects, drug therapy, effects, Gastric, Gastric Acid, Gastric Acidity Determination, GASTRIN, Gastrins, HEALTHY, Hydrogen-Ion Concentration, INCREASES, inhibition, Male, MED, metabolism, Methods, MG, pH, PLACEBO, PLACEBO CONTROLLED TRIAL, plasma, RANDOMIZED CONTROLLED TRIAL, response, secretion, Stomach Ulcer, Support, Non-U.S.Gov't, therapeutic use, TIME, Treatment Outcome, TRIAL, VARIABILITY, VS, ACID, AGENTS, gastroenterology, UK
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)

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