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

Abstract

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 pi-I 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 t( 1/4 ) 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.