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.

Background: Rabeprazole (LY307640, E3810) is a new, potent, proton pump inh ibitor, A single daily 20 mg dose significantly decreases 24-h intragastric acidity. There are no data currently available directly comparing the effe ct 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 ran domized, double-blind, placebo-controlled trial, in healthy H. pylori-negat ive subjects, Methods: Twenty-four healthy male volunteers, negative for H. pylori infect ion by serology and C-13-urea breath test, were studied on the Ist and 8th day of dosing with either placebo, rabeprazole 20 mg or omeprazole 20 mg, o nce each morning, in a crossover fashion. On days 1 and 8, hourly intragast ric acidity was measured by gastric aspiration for 24 h from 08.00 hours. O n 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 dec reased 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, P < 0.001), resulting in a significantly higher med ian 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 s tatistically significant (160 vs, 218 mmol,h/L, P = 0.1). However, 24-h pla sma gastrin concentration (1687 vs. 1085 pmol.h/L, P < 0.01) and percentage time that intragastric pH was > 3 (69 vs. 59%, P = 0.008) and >4 (60 vs. 5 1%, P = 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 th e differences in intragastric pH > 3 and > 4 holding times persisted, but t here was no significant difference in 24-h acidity.