Bioequivalence Study of 2 Formulations of Film-coated Tablets containing a Fixed Dose Combination of Bisoprolol Fumarate 5 mg and Hydrochlorothiazide 6.25 mg in Healthy Subjects

Abstract

Background:

The present study was conducted to compare the bioavailability of 2 formulations of fixed-dose combination of bisoprolol fumarate 5 mg and hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (test and reference formulations).

Methods:

This study was a randomized, single-blind, 2-period, 2-sequence cross-over study which included 18 healthy adult male and female subjects under fasting condition. The pharmacokinetic parameters, AUC_t, AUC_inf, C_max, t_max, and t_½ were determined based on the concentrations of bisoprolol (CAS 66722-44-9) and HCT (CAS 58-93-5), using ultra-performance liquid chromatography with tandem mass spectrometer detector (UPLC-MS/MS). In each of the 2 study periods (with a washout of 1 week) a single dose of test or reference product was administered.

Results:

The geometric mean ratios (90% CI) of the test drug/reference drug for bisoprolol were 97.22% (93.75–100.83%) for AUC_t(0-48), 97.20% (93.97–100.54%) for AUC_inf, and 100.36% (93.83–107.34%) for C_max; while those for HCT were 93.22% (84.72–102.57%), 93.39% (85.43–102.10%) and 99.39% (85.45–115.61%), for AUC_t(0–24), AUC_inf, and C_max, respectively. The differences between the test and reference drug products for tmax values of bisoprolol as well as t_½ values of both bisoprolol and hydrochlorothiazide were not statistically significant; yet, the difference was statistically significant for the tmax values of hydrochlorothiazide. There was no adverse event encountered during this bioequivalence test.

Major conclusion:

It was concluded that the 2 formulations of fixed dose combination of bisoprolol fumarate 5 mg and hydrochlorotiazide (HCT) 6.25 mg film-coated tablet (the test and reference products) were bioequivalent.

Key words

β1-adrenergic receptor antagonist - bioequivalence - bisoprolol - diuretic - hydrochlorothiazide - pharmacokinetics

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