A placebo-controlled trial to assess the effects of 8 days of dosing with rabeprazole versus omeprazole on 24-h intragastric acidity and plasma gastrin concentrations in young healthy male subjects

Authors


Pounder Centre for Gastroenterology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. E-mail: pounder@rfhsm.ac.uk

Abstract

Background:

Rabeprazole (LY307640, E3810) is a new, potent, proton pump inhibitor. A single daily 20 mg dose significantly decreases 24-h intragastric acidity. There are no data currently available directly comparing the effect of rabeprazole on 24-h acidity with established proton pump inhibitors.

Aim:

To compare the effects of rabeprazole 20 mg o.m. and omeprazole 20 mg o.m. on 24-h intragastric acidity and plasma gastrin concentration in a randomized, double-blind, placebo-controlled trial, in healthy H. pylori-negative subjects.

Methods:

Twenty-four healthy male volunteers, negative for H. pylori infection by serology and 13C-urea breath test, were studied on the 1st and 8th day of dosing with either placebo, rabeprazole 20 mg or omeprazole 20 mg, once each morning, in a crossover fashion. On days 1 and 8, hourly intragastric acidity was measured by gastric aspiration for 24 h from 08.00 hours. On day 8, plasma gastrin concentrations were also measured hourly from 08.00 to 24.00 hours, then every 2 h thereafter.

Results:

A single dose of both rabeprazole and omeprazole significantly decreased 24-h intragastric acidity compared with placebo. The 24-h acidity on day 1 was significantly decreased for rabeprazole compared with omeprazole (331 vs. 640 mmol.h/L, < 0.001), resulting in a significantly higher median 24-h intragastric pH and longer times at which intragastric pH was>  3 and>  4. On day 8 of dosing, the decrease in 24-h intragastric acidity was greater with rabeprazole than with omeprazole, but the difference was not statistically significant (160 vs. 218 mmol.h/L, = 0.1). However, 24-h plasma gastrin concentration (1687 vs. 1085 pmol.h/L, < 0.01) and percentage time that intragastric pH was>  3 (69 vs. 59%, = 0.008) and>  4 (60 vs. 51%, = 0.03) were significantly greater.

Conclusions:

Rabeprazole 20 mg once daily has a significantly faster onset of antisecretory activity than omeprazole 20 mg once daily. After 8 days the differences in intragastric pH > 3 and>  4 holding times persisted, but there was no significant difference in 24-h acidity.

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