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.

R R Tjandrawinata, E Setiawati, D A Yunaidi, I D Santoso, A Setiawati, L W Susanto

Index: Drug Res. (Stuttg.) 63(5) , 243-9, (2013)

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Abstract

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).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, AUCt, AUCinf, Cmax, tmax, and t½ 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.The geometric mean ratios (90% CI) of the test drug/reference drug for bisoprolol were 97.22% (93.75-100.83%) for AUCt(0-48), 97.20% (93.97-100.54%) for AUCinf, and 100.36% (93.83-107.34%) for Cmax; 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 AUCt(0-24), AUCinf, and Cmax, respectively. The differences between the test and reference drug products for tmax values of bisoprolol as well as t½ 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.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.© Georg Thieme Verlag KG Stuttgart · New York.