title: 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, 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dexa Laboratories of Biomolecular Sciences (DLBS), Cikarang, Indonesia.
authors.forename: R R
authors.initials: RR
authors.lastname: Tjandrawinata
authors.forename: E
authors.initials: E
authors.lastname: Setiawati
authors.forename: D A
authors.initials: DA
authors.lastname: Yunaidi
authors.forename: I D
authors.initials: ID
authors.lastname: Santoso
authors.forename: A
authors.initials: A
authors.lastname: Setiawati
authors.forename: L W
authors.initials: LW
authors.lastname: Susanto
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017298:Bisoprolol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D016037:Single-Blind Method; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D013607:Tablets; D006852:Hydrochlorothiazide; D017298:Bisoprolol