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DOI: 10.1055/s-0032-1331768
Bioequivalence and Pharmacokinetic Evaluation of Two Tablet Formulations of Carvedilol 25-mg: A Single-Dose, Randomized-Sequence, Open-Label, Two-Way Crossover Study in Healthy Chinese Male Volunteers
Publikationsverlauf
received 24. August 2012
accepted 03. Dezember 2012
Publikationsdatum:
17. Januar 2013 (online)
![](https://www.thieme-connect.de/media/drugres/201302/lookinside/thumbnails/10.1055-s-0032-1331768-1.jpg)
Abstract
Background:
Carvedilol is a nonselective-blocking agent and is used in the treatment of hypertension and angina pectoris.
Objective:
The aim of this study was to evaluate bioequivalence of two 25-mg tablet formulations of carvedilol following single oral dose in adult male volunteers.
Methods:
This was a randomized, single-dose, open-label, crossover bioequivalence study. Plasma samples were collected before dosing and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 h after dosing. Plasma concentrations of Carvedilol were determined by using a validated LC-MS/MS method. Statistical analysis of the pharmacokinetic parameters Cmax, AUC0–24, and AUC0–∞ was conducted to determine bioequivalence.
Results:
23 healthy male Chinese volunteers were enrolled in the study. The mean (SD) Cmax, AUC0–24, and AUC0–∞ values after administration of the test and reference formulations, respectively, were as follows: 73.71 (34.04) vs. 78.93 (43.64) ng/mL, 285.1 (147.0) vs. 296.9 (176.1) ng/mL · h, and 296.5 (161.4) vs. 303.4 (177.9) ng/mL · h. The 90% CIs of the ratios (test vs. reference) for the ln-transformed Cmax, AUC0–24, and AUC0 − ∞ were 85.3% to 114.3%, 90.4% to 107.6%, and 90.9% to108.4%, respectively, meeting the criteria of SFDA, FDA and EMEA for bioequivalence. The relative bioavailability of the test formulation to reference formulation was 100.1%. Both formulations were generally well tolerated and no serious AEs were reported in the study.
Conclusions:
The 90% CIs for the ratios of mean Cmax, AUC0–24, and AUC0–∞ met the regulatory criteria for bioequivalence.
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