Comparative Fasting Bioavailability of 2 Bepotastine Formulations in Healthy Male Chinese Volunteers: An Open-Label, Randomized, Single-Dose, 2-Way Crossover Study

Background: Bepotastine is a second-generation histarninei receptor antagonist that is used in the treatment of allergic rhinitis, urticaria, and pruritus associated with skin disease. A new generic formulation of bepotastine has been developed in China, and information concerning bioavailability and pharmacokinetic properties in the Chinese population has not been reported. Objective: The aim of the present study was to compare the bioavailability and pharmacokinetic properties of 2 tablet formulations of bepotastine, the 10-mg generic formulation (test) and a branded formulation (reference), in healthy male Chinese volunteers to obtain registration approval of the test formulation. Methods: A single-center,. open-label, randomized, 2-way crossover study with a 1-week washout period was conducted in 24 healthy male volunteers. Blood samples were collected for 16 hours after a single dose of the 10-mg bepotastine test formulation or the reference formulation. Plasma bepotastine concentrations were determined using a validated LC-MS/MS method. C-max, T-max, AUC(0-t), AUC(0-infinity), and t(1/2), were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for the log-transformed C-max and AUC values were within the predetermined interval of 75% to 133% and 80% to 125%, respectively, according to the guidelines of the China Food and Drug Administration. Results: No significant differences were found in mean (SD) pharmacokinetic parameters between the test and reference drugs, including C-max (74.81 [9.91] ng/mL vs 78.60 [29.58] ng/mL), AUC(0-t) (295.55 [115.29] ng center dot h/mL vs 299.17[109.29] ng center dot h/mL), and AUC(0-infinity), (305.28 [118.50] ng center dot h/mL vs 310.90 [112.20] ng center dot h/mL). The mean (SD) t1/2 values of the test and reference formulations were 2.53 (0.50) hours and 2.62 (0.41) hours, respectively. The 90% CIs of the treatment ratios for the logarithmic transformed values of Cma, AUC(0-t), and AUC(0-infinity) were 86.96% to 101.80%, 93.22% to 104.13%, and 92.66% to 103.30%, respectively. All values were within the predetermined bioequivalence range. Two adverse events were reported as neutropenia (1 volunteer [4.2%]) and neutrophilia (1 volunteer [4.2%]). Both adverse events were transient and considered mild by physicians. Conclusion: The test and reference tablets met the regulatory criteria for bioequivalence as defined by the China Food and Drug Administration. Both formulations were well tolerated. Chinese Clinical Trials Registry identifier: ChiCTR-TTRC C-13003723. (C) 2014 Published by Elsevier HS Journals, Inc.