BACKGROUND Rebamipide is a quinolinone-derived gastroprotective agent approved in Korea for the treatment of gastric ulcers, acute gastritis, and exacerbated chronic gastritis. OBJECTIVE The aims of this study were to evaluate the pharmacokinetics and bioequivalence of a reference (branded) and test (generic) formulation of rebamipide 100-mg tablets in healthy Korean male volunteers for the purposes of generic substitution and to evaluate the relationship between genetic polymorphisms in the ABCB1 gene (exons 21 and 26) and rebamipide pharmacokinetics. METHODS This study had a 2-period crossover design, with a 7-day washout between formulations. Healthy Korean male volunteers were randomly assigned to receive a single 100-mg dose of the test or reference formulation, administered with 240 mL of water after a 12-hour overnight fast. Serum concentrations of rebamipide up to 12 hours after administration were determined using a validated HPLC method with fluorescence detection. Vital signs (temperature, blood pressure, and heart rate) were measured before and after dosing in both periods. Adverse events were monitored by clinic staff on the days of study drug administration and were recorded for up to 1 week after the last dose of study medication. Pharmacokinetic parameters were determined using a noncompartmental method. The formulations were considered bioequivalent if the log-transformed ratios of AUC(0-t), AUC(0-infinity)), and C(max) were within the predetermined bioequivalence range (80%-125%) established by the US Food and Drug Administration and Korean legislation. The in vitro dissolution profiles of the 2 formulations were examined, and the influence on rebamipide pharmacokinetics of genetic polymorphisms in the ABCB1 gene (P-glycoprotein) was investigated. RESULTS Thirty healthy Korean male volunteers (mean [SD] age, 22.97 [1.67] years [range, 20-27 years]; height, 174.56 [6.27] cm [range, 159.1-184.8 cm]; and weight, 69.44 [8.32] kg [range, 54.7-90.2 kg]) were enrolled in and completed the study. No adverse events were reported. The 2 formulations had comparable in vitro dissolution profiles. The mean AUC(0-t) for the test and reference formulations was 831.09 (329.52) and 903.46 (419.17) ng/mL/h, respectively; the AUC(0-infinity) was 851.68 (332.62) and 923.58 (423.21) ng/mL/h; the C(max) was 218.12 (93.90) and 220.57 (107.48) ng/mL; the T(max) was 2.05 (1.15) and 2.10 (0.76) hours; and the t((1/2)) was 1.96 (0.52) and 1.93 (0.49) hours. No significant sequence, subject, formulation, or period effects were detected for any pharmacokinetic parameter. The point estimates for AUC(0-t), AUC(0-infinity), and C(max) were 0.95 (90% CI, 0.84-1.06), 0.95 (90% CI, 0.84-1.06), and 1.01 (90% CI, 0.89-1.15), respectively, satisfying the criterion for bioequivalence. There was no statistically significant difference in T(max). No significant differences in rebamipide AUC(0-t), AUC(0-infinity), or C(max) were found among the ABCB1 2677 GG, GT, or TT groups, or among the ABCB1 3435 CC, CT, or TT groups. There was no evidence that genetic polymorphisms in the ABCB1 gene influenced the pharmacokinetics of rebamipide. CONCLUSIONS The results of this study in healthy Korean male volunteers suggest that the 2 rebamipide 100-mg tablet formulations administered in the fasted state met the regulatory criterion for bioequivalence. There was no evidence that rebamipide pharmacokinetic parameters were influenced by genetic polymorphisms in the ABCB1 gene (exons 21 and 26). ClinicalTrials.gov identifier: .