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

• Published in: Alimentary pharmacology & therapeutics Vol. 14; no. 6; pp. 691 - 699
• Main Authors: WILLIAMS, M. P, BLANSHARD, C, MILLSON, C, SERCOMBE, J, POUNDER, R. E
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01.06.2000; Blackwell
• Subjects: 2-Pyridinylmethylsulfinylbenzimidazoles; Adult; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - therapeutic use; Benzimidazoles - administration & dosage; Benzimidazoles - therapeutic use; Biological and medical sciences; Cross-Over Studies; Digestive system; Double-Blind Method; Gastric Acid - metabolism; Gastric Acidity Determination; Gastrins - blood; Gastrins - drug effects; Humans; Hydrogen-Ion Concentration; Male; Medical sciences; Omeprazole - analogs & derivatives; Pharmacology. Drug treatments; Rabeprazole; Stomach Ulcer - drug therapy; Treatment Outcome; Multiple dose; Human; Stomach; Healthy subject; Benzimidazole derivatives; Gastrin; pH; Rabeprazole; Proton pump inhibitor; Blood plasma; Dose activity relation
• DOI: 10.1046/j.1365-2036.2000.00772.x
• ISSN: 0269-2813

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.