Background and objective: Bepotastine is a second-generation histamine H(1) receptor antagonist that is indicated in allergic rhinitis, urticaria, and pruritus associated with skin disease. The aim of the present study was to compare the pharmacokinetics of two different bepotastine formulations [bepotastine besilate 10 mg (reference) and bepotastine salicylate 9.64 mg (test)], both containing 7.11 mg bepotastine base, to satisfy regulatory requirements for marketing.
Methods: A single-center, randomized, single-dose, open-label, two-period, two-sequence crossover study with a 7-day washout period was conducted in 26 healthy male subjects. Plasma samples for drug analysis were collected up to 24 h after drug treatment. Pharmacokinetic parameters, including maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC), were calculated. ANOVA for bioequivalence was conducted using log-transformed C(max) and AUC values, and the mean ratios and their 90 % confidence intervals were calculated.
Results: Of the 26 participants initially enrolled, 24 healthy participants completed both treatment periods. All pharmacokinetic parameters of bepotastine exhibited no significant differences between the two formulations. The observed mean (standard deviation) C(max), AUC from time zero to the time of the last measurable concentration (AUC(last)), and AUC from time zero to infinity (AUC(∞)) values for the reference formulation were 99.9 (31.4) ng/mL, 388.9 (102.6) ng·h/mL, and 392.4 (103.6) ng·h/mL, respectively. Corresponding values for the test formulation were 101.0 (26.3) ng/mL, 389.8 (112.2) ng·h/mL, and 393.7 (111.7) ng·h/mL. The geometric mean ratios (90 % CI) between the two formulations were 1.0220 (0.9224-1.1324) for C(max), 0.9928 (0.9521-1.0351) for AUC(last), and 0.9959 (0.9549-1.0387) for AUC(∞). During the study period, two adverse events were reported in the test formulation group, but both were transient, mild, and resolved completely during the treatment period. These adverse events were considered unrelated to the study drugs.
Conclusion: The results of the present study revealed that bepotastine besilate 10 mg (reference) and bepotastine salicylate 9.64 mg (test) formulations have comparable pharmacokinetic characteristics and that these two formulations meet the regulatory criteria for bioequivalence. Both bepotastine formulations were generally well-tolerated in this population.
Trial registration: ClinicalTrials.gov NCT01897428.