An ascending single-dose safety and tolerance study of an oral formulation of rabeprazole (E3810).

BACKGROUND

Proton pump inhibitors such as omeprazole produce a long-lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin. Rabeprazole (E3810) is a new substituted benzimidazole H+,K+ ATPase inhibitor. It acts as an irreversible, non-competitive inhibitor of the H+,K+ ATPase and preliminary studies demonstrate that rabeprazole produces a potent and long-lasting inhibition of gastric acid secretion and a low level of hypergastrinaemia.

AIM

This randomized, double-blind, placebo-controlled study was performed to further examine the effects of different single doses of rabeprazole on gastric acid secretion and serum gastrin.

METHODS

In this study, four groups of 10 healthy, non-smoking Helicobacter pylori-negative men (mean age 22.5 +/- 3.9 years) received single oral doses of 10, 20, 30 and 40 mg of rabeprazole. Two of the 10 volunteers in each group received placebo as part of the double-blind study design. All volunteers who entered into the study had a normal gastric acid secretory capacity as evaluated by pentagastrin challenge. Prior to administration of the first dose of test drug, volunteers underwent an inpatient 24-h measurement of baseline intragastric pH. One week later, volunteers received the test drug and again underwent an inpatient 24-h measurement of intragastric pH. During both periods, plasma samples were collected at specified intervals over 48 h and were sent for analysis of rabeprazole and gastrin levels.

RESULTS

Administration of rabeprazole resulted in a dose-dependent increase in the duration and extent of intragastric pH elevation. The response among all volunteers receiving drug was significantly different from placebo, with greater acid inhibition occurring in the 30 and 40 mg groups. In addition, there was also a dose-related increase in plasma gastrin. The pharmacokinetics of rabeprazole were similar to those of other proton pump inhibitors with a t1/2 of between 0.7 and 1.0 h. There were no clinically significant effects on patient laboratory tests or serious adverse events.

CONCLUSIONS

The results of this study suggest that rabeprazole is as potent as omeprazole and lansoprazole in inhibiting gastric acid secretion.