title: Bioequivalence study of 2.5 mg film-coated bisoprolol tablets in healthy volunteers.
abstract: BACKGROUND
  Bisoprolol is one of the most widely used beta-blockers characterised by cardioselectivity, and it has no intrinsic sympathomimetic activity. It is commonly used in the treatment of coronary heart disease and heart failure.
  
  
  OBJECTIVE
  The aim of study was to assess the bioequivalence of the film-coated tablets containing 2.5 mg of bisoprolol (Bisocard® - the medicinal product) to the original medicinal product (Concor Cor 2.5® - the reference).
  
  
  METHODS
  A randomised, open-label, two-period, crossover, single-dose, relative bioavailability study was conducted in fasted healthy Caucasian volunteers. A single 10-mg oral dose (four tablets of 2.5 mg) of the test or reference product was followed by a 14-day wash-out period, after which the subjects received the alternative product. Blood was sampled within a period of 60 h post administration in pre-specified time points. Bisoprolol concentrations were determined by a validated LC-MS/MS method. The products were considered bioequivalent if the 90% confidence interval (CI) of the log-transformed geometric mean ratios (test vs. reference) for AUC(0-t), AUC(0-∞), and Cmax were within 80-125% limits. Adverse events were monitored during the study based on the subject claims and clinical parameters.
  
  
  RESULTS
  Twenty-six healthy male and female volunteers (mean age ca. 29 years; body mass index 22.7 kg/m²) were in-cluded in the study, and 24 completed the clinical part. The geometric mean ratios (test/reference) for the log-transformed AUC(0-t), AUC(0-∞), and Cmax were 95.16% (90% CI 92.52-97.87%), 95.08% (90% CI 92.40-97.83%), and 100.00% (90% CI 94.83-105.45%), respectively. There were no significant differences in the pharmacokinetic parameters between the test and reference formulations. No serious adverse events were reported.
  
  
  CONCLUSIONS
  The results of this single-dose study in healthy Caucasian volunteers indicate that Bisocard®; 2.5 mg film-coated tablets are bioequivalent to the reference product - Concor Cor 2.5®; 2.5 mg film-coated tablets. Both products had similar safety profile and have been well tolerated.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Buś-Kwaśnik
authors.affiliation: Pharmacology Department, Pharmaceutical Research Institute, Warsaw, Poland. p.rudzki@ifarm.eu.
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Rudzki
authors.forename: Hanna
authors.initials: H
authors.lastname: Ksycińska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Leś
authors.forename: Krystyna
authors.initials: K
authors.lastname: Serafin-Byczak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Raszek
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bielak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wybraniec
authors.forename: Anna E
authors.initials: AE
authors.lastname: Płatek
authors.forename: Filip M
authors.initials: FM
authors.lastname: Szymański
authors.forename: Tomasz
authors.initials: T
authors.lastname: Łazowski
mesh_terms: D000293:Adolescent; D000328:Adult; D001682:Biological Availability; D017298:Bisoprolol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002853:Chromatography, Liquid; D003327:Coronary Disease / Q000188:drug therapy; D018592:Cross-Over Studies; D004339:Drug Compounding; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D044465:White People; D055815:Young Adult
chemical_list: D013607:Tablets; D017298:Bisoprolol
keywords: beta-blocker; bioequivalence; bisoprolol; pharmacokinetics; relative bioavailability