Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects

Abstract

Background

The present study was conducted to compare the bioavailability of two bisoprolol fumarate 5 mg film-coated tablet formulations (test and reference formulations).

Patients and methods

This study was a randomized, single-blind, two-period, two-sequence crossover study that included 18 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters were determined based on the concentrations of bisoprolol (CAS 66722-44-9), using ultraperformance liquid chromatography with a tandem mass spectrometer detector. In each of the two study periods (separated by a washout of 1 week) a single dose of test or reference product was administered. The pharmacokinetic parameters assessed were area under the plasma concentration-time curve from time zero to 48 hours (AUC_t), AUC from time zero to infinity (AUC_inf), the peak plasma concentration of the drug (C_max), time needed to achieve C_max (t_max), and the elimination half-life (t_½).

Results

The geometric mean ratios (90% confidence intervals) of the test drug/reference drug for bisoprolol were 101.61% (96.14%–107.38%) for AUC_t, 101.31% (95.66%–107.29%) for AUC_inf, and 100.28% (93.90%–107.09%) for C_max. The differences between the test and reference drug products for bisoprolol t_max and t_½ values were not statistically significant (P > 0.05). There was no adverse event encountered during this bioequivalence test. The 90% confidence intervals of the test/reference AUC ratio and C_max ratio of bisoprolol were within the acceptance range for bioequivalence.

Conclusion

It was concluded that the two bisoprolol film-coated tablet formulations (the test and reference products) were bioequivalent in terms of the rate and extent of absorption.

Keywords:

• β1-adrenergic receptor antagonist
• antihypertension
• bioavailability
• bioequivalence
• bisoprolol
• pharmacokinetics

Acknowledgments

We deeply thank the volunteers for their participation in this study. The assistance of Putuwitia Pramihadarini, Pharm, in preparing the study report is gratefully appreciated.

Disclosure

The authors declare no competing interests in connection with the contents of this manuscript.