title: Comparative fasting bioavailability of 2 bepotastine formulations in healthy male Chinese volunteers: an open-label, randomized, single-dose, 2-way crossover study.
abstract: BACKGROUND
  Bepotastine is a second-generation histamine1 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. Cmax, Tmax, AUC₀-t, AUC₀-∞, and t½ were determined using noncompartmental analysis. The formulations were considered bioequivalent if the 90% CIs for the log-transformed Cmax 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 Cmax (74.81 [9.91] ng/mL vs 78.60 [29.58] ng/mL), AUC₀-t (295.55[115.29] ng·h/mL vs 299.17[109.29] ng·h/mL), and AUC0-∞ (305.28 [118.50] ng·h/mL vs 310.90 [112.20] ng·h/mL). The mean (SD) t½ 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 Cmax, AUC₀-t, and AUC₀-∞ 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.
  
  
  CONCLUSIONS
  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-TTRCC-13003723.
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China. Electronic address: stjz@zju.edu.cn.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shentu
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Huili
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xingjiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Guolan
authors.initials: G
authors.lastname: Wu
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wu
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Meixiang
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yunliang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Research Center of Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002681:China; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics; D005215:Fasting / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics*; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics*; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods; D013810:Therapeutic Equivalency; D014481:United States; D055815:Young Adult
chemical_list: D016568:Drugs, Generic; D010880:Piperidines; D011725:Pyridines; D013607:Tablets; C108476:bepotastine
keywords: LC-MS/MS; bepotastine; bioequivalence; human plasma; pharmacokinetics