title: Bioequivalence study of two different tablet formulations of carvedilol in healthy volunteers.
abstract: OBJECTIVE
  The aim of this study was to compare the extent and rate of absorption of two different carvedilol (CAS 72956-09-3) tablet formulations: 25 mg tablets, as the test formulation and the reference innovator product (25 mg tablets).
  
  
  METHODS
  This study was designed as a single-dose, open-label, randomised, with a two-period and two-sequence crossover design, with blind determination of drug plasma concentration and a minimum 7-day washout period. Twenty-four healthy volunteers of both sexes were randomly assigned to treatment sequences. Carvedilol concentrations were determined in plasma samples obtained over a 24-h interval: baseline (pre-administration) and at 14 different times within the 24 h after administration. The analytical method, which used HPLC coupled with a MS/MS detector, was duly validated and the analytical assay was performed in compliance with Good Laboratory Practice (GLP). The limit of quantification (LOQ) was 0.50 ng/mL. Pharmacokinetic parameters representing the extent and/or rate of absorption (AUCinf, AUClast, and Cmax) were obtained. As secondary objective the tolerability of both formulations was also evaluated.
  
  
  RESULTS
  The geometric mean of the test/reference formulations individual percent ratio was 98.14 % for AUCinf, 98.44 % for AUClast and 98.39 % for Cmax. The 90 % CI for the geometric mean of the individual ratio test/references formulations was 95.13 to 101.24 % for AUCinf, 95.23 to 101.76 % for AUClast, and 88.26 to 109.67 % for Cmax.
  
  
  CONCLUSIONS
  The 90 % CI values obtained for AUCinf, AUClast, and Cmax are within the interval proposed by the EMEA/CPMP and the FDA as bioequivalence acceptance criteria, and consequently it can be conclude that the test formulation is bioequivalent with the reference formulation both in terms of rate and extent of absorption after single dose administration. The results from a previous pilot study allowed an optimal design for this trial.
authors.affiliation: Servicio de Farmacología Clínica, Hospital Clinico San Carlos, Madrid (Spain).
authors.forename: Antonio
authors.initials: A
authors.lastname: Portolés
authors.forename: Augusto
authors.initials: A
authors.lastname: Filipe
authors.forename: Susana
authors.initials: S
authors.lastname: Almeida
authors.forename: Ana
authors.initials: A
authors.lastname: Terleira
authors.forename: François
authors.initials: F
authors.lastname: Vallée
authors.forename: Emilio
authors.initials: E
authors.lastname: Vargas
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000328:Adult; D019540:Area Under Curve; D002138:Calibration; D002227:Carbazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D013607:Tablets; D000077261:Carvedilol