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 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.


OBJECTIVE
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, P < 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, P = 0.1). However, 24-h plasma 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. 51%, 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 the differences in intragastric pH > 3 and > 4 holding times persisted, but there was no significant difference in 24-h acidity.
Williams
M P
MP
University Department of Medicine, Royal Free and University College Medical School, London, UK.
Sercombe
J
J
Hamilton
M I
MI
Pounder
R E
RE
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D005755:Gastrins / Q000097:blood*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology*; D064750:Rabeprazole; D011863:Radioimmunoassay; D018709:Statistics, Nonparametric
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D005755:Gastrins; D064750:Rabeprazole; D000251:Adenosine Triphosphatases; D009853:Omeprazole