Pharmacokinetic comparisons of bepotastine besilate and bepotastine salicylate in healthy subjects

Kyoung Ah Kim, Ji-Young Park

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background and Objective: Bepotastine is a second-generation histamine H1 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 (AUClast), 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.

Original languageEnglish
Pages (from-to)913-919
Number of pages7
JournalClinical Drug Investigation
Volume33
Issue number12
DOIs
Publication statusPublished - 2013 Dec 1

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Salicylates
Area Under Curve
Healthy Volunteers
Pharmacokinetics
Therapeutic Equivalency
Pharmaceutical Preparations
Histamine H1 Antagonists
Urticaria
Pruritus
bepotastine
bepotastine besilate
Marketing
Skin Diseases
Cross-Over Studies
Analysis of Variance
Reference Values
Therapeutics
Confidence Intervals
Population

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Pharmacokinetic comparisons of bepotastine besilate and bepotastine salicylate in healthy subjects. / Kim, Kyoung Ah; Park, Ji-Young.

In: Clinical Drug Investigation, Vol. 33, No. 12, 01.12.2013, p. 913-919.

Research output: Contribution to journalArticle

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title = "Pharmacokinetic comparisons of bepotastine besilate and bepotastine salicylate in healthy subjects",
abstract = "Background and Objective: Bepotastine is a second-generation histamine H1 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 (AUClast), 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.",
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N2 - Background and Objective: Bepotastine is a second-generation histamine H1 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 (AUClast), 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.

AB - Background and Objective: Bepotastine is a second-generation histamine H1 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 (AUClast), 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.

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