Pharmacokinetics and Bioequivalence Study of Two Cetirizine Hydrochloride Formulations in Healthy Chinese Male Volunteers

Feng-Guo Xu; Ying Liu; Zun-Jian Zhang; Yuan Tian; Yun Chen

doi:10.1055/s-0031-1296422

Arzneimittelforschung, Table of Contents

Arzneimittelforschung 2009; 59(9): 440-444
DOI: 10.1055/s-0031-1296422

Antiallergic Drugs · Antiasthmatics · Antitussives · Bronchodilators · Bronchosecretogogues · Mucolytics

Editio Cantor Verlag Aulendorf (Germany)

Pharmacokinetics and Bioequivalence Study of Two Cetirizine Hydrochloride Formulations in Healthy Chinese Male Volunteers

Feng-Guo Xu

¹Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing (The People’s Republic of China)

²Center for Instrumental Analysis, China Pharmaceutical University, Nanjing (The People’s Republic of China)

,

Ying Liu

³Department of Pharmacy, Nanjing Municipal Hospital of TCM, Nanjing (The People’s Republic of China)

,

Zun-Jian Zhang

¹Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing (The People’s Republic of China)

²Center for Instrumental Analysis, China Pharmaceutical University, Nanjing (The People’s Republic of China)

,

Yuan Tian

¹Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing (The People’s Republic of China)

²Center for Instrumental Analysis, China Pharmaceutical University, Nanjing (The People’s Republic of China)

,

Yun Chen

⁴Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing (The People’s Republic of China)

› Author Affiliations

Abstract

The pharmacokinetics and relative bio-availability/bioequivalence of two formulations of cetirizine hydrochloride (CAS 83881-51-0) were assessed in this paper. Using a two-treatment, two-period, two-sequence, randomized crossover design, test and reference formulations were administered as individual single doses to 18 Chinese healthy male volunteers under non-fed conditions, with a 7-day washout period between dosing. Fourteen blood samples were drawn from each subject over a 34-h period. Cetirizine concentrations in plasma were determined by a validated high performance liquid chromatographic-ultraviolet (HPLC/UV) assay, and pharmacokinetic parameters, C_max, AUC_0–t, AUC_0–∞ and t_1/2 were calculated from the plasma concentration-time data of each individual and during each period by applying non-compartmental analysis. Pharmacokinetic data for test and reference formulations were analyzed statistically to test for bioequivalence of the two formulations. After oral administration the values of C_max, t_max, t_1/2, MRT, AUC_0–t, AUC_0–∞ for test and reference formulations were 0.80 ± 0.14 and 0.80 ± 0.23 µg/ml, 0.8 ± 0.4 and 1.1 ± 0.7 h, 7.59 ± 0.68 and 7.63 ± 0.93 h, 10.59 ± 0.94 and 10.92 ± 1.26 h, 6.00 ± 1.04 and 5.98 ± 1.39 µg · h/ml, respectively. ANOVA and CI test showed no significant (p > 0.05) variation in these pharmacokinetic parameters of test and reference formulations. When the AUC_0–t values for both formulations for natural log-transformed data were compared, the test formulation showed a bioavailability of 100.9 ± 7.7%, as compared to the reference formulation. These values are within the acceptance limit of 80–125%. No adverse events were observed in any of the subjects during the two runs of the study. Both clinical and laboratory parameters of all subjects showed no clinically significant changes. This study shows that both formulations were well tolerated and the test formulation can be considered a pharmaceutically and therapeutically equivalent alternative to the reference formulation.

Key words

Antihistamine - CAS 83881-51-0 - Cetirizine hydrochloride, bioequivalence, pharmacokinetics

Full Text

References

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