Bioequivalence of rebamipide granules and tablets in healthy adult male volunteers.

OBJECTIVE

Rebamipide tablets, which are used in the treatment of patients with gastric ulcers or gastritis, can be difficult to administer in subjects with reduced swallowing ability or impaired swallowing. The granule formulation may be more easily administered in these patients. The bioequivalence between rebamipide granules (20%/0.5g) and tablets (100mg) was determined in healthy male adult volunteers, in accordance with the Partially Revised Guidelines for Bioequivalence Studies of Generic Products.

STUDY DESIGN

In a randomised, nonblind, crossover design, 28 individuals were allocated into two groups of 14 to receive either rebamipide granules or rebamipide tablets. Each individual, under fasting conditions, was administered a single oral dose of rebamipide 100mg followed by a 7-day washout period. Individuals then received a single oral dose of the other rebamipide formulation. Blood samples were collected at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours. Plasma rebamipide concentrations were measured by validated high-performance liquid chromatography with tandem mass spectrometry.

RESULTS

The plasma concentration-time profiles and pharmacokinetic parameters of rebamipide after administration of the granule formulation were similar to those of the tablet in 27 healthy male volunteers. Following administration of the granule formulation, the area under the plasma concentration-time curve from time 0-24 hours (AUC(24h)) was 912.82 mug/L . h, the maximum plasma concentration (C(max)) was 241.82 mug/L, time to maximum plasma concentration (t(max)) was 2.5 hours, and plasma elimination half-life (t((1/2))) was 1.97 hours. Corresponding values for the tablet formulation were 873.55 microg/L . h, 216.19 mug/L, 2.4 hours, and 1.94 hours. The difference in mean log values was 1.01 for AUC(24h) and 1.09 for C(max) after granule and tablet administration. The 90% confidence interval of this difference in mean log value was 0.93-1.10 for AUC(24h), and 0.97-1.21 for C(max). This satisfies the criteria for bioequivalence in the guidelines [within log (0.8) to log (1.25)].

CONCLUSIONS

Rebamipide granules (20%/0.5g) and tablet (100mg) were bioequivalent. Rebamipide granules may therefore be a more practical treatment option in patients with gastric ulcers or gastritis who have difficulty swallowing tablets.