Comparative bioavailability study with two amiodarone tablet formulations administered with and without food in healthy subjects.
OBJECTIVE
The aim was to assess the comparative bioavailability of two formulations (200 mg tablet) of amiodarone (CAS 19774-82-4) in healthy volunteers of both sexes, with and without food.


METHODS
The study was conducted using an open, randomized, two-period crossover design with a 3-week washout interval, in two groups, with and without food. Plasma samples were obtained for up to 240 h post dose. Plasma amiodarone concentrations were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM). From the amiodarone plasma concentration vs. time curves, the following pharmacokinetic parameters were obtained, with and without food: AUC(last), AUC(inf), AUC(0-240h), AUC(0-72h) and C(max).


RESULTS
The limit of quantification was 1 ng/mL for plasma amiodarone analysis. The geometric mean and 90% confidence interval CI of Test/Reference percent ratios were, without and with food, respectively: 107.61 (92.73-124.89) and 100.6 (94.1-107.5) for C(max), 107.05 (95.88-119.51) and 100.2 (96.0-104.7) for AUC(last), 107.27 (95.78-120.15) and 100.8 (97.0-104.8) for AUC(0-72h), 106.76 (95.84-118.94) and 100.2 (96.0-104.7) for AUC(0-240h) and AUC(inf) 105.15 (94.18-117.41) and 100.7 (96.6-105.0).


CONCLUSIONS
Since the 90% CI for AUC(0-72) and C(max) ratios were within the 80-125% interval proposed by the US FDA, it was concluded that the amiodarone 200 mg tablet (test formulation) with and without food was bioequivalent to the reference 200 mg tablet for both the rate and extent of absorption.
dos Santos Filho
Hilton Oliveira
HO
Cartesius Analytical Unit, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Ilha
Jaime O
JO
Silva
Lara Cristina
LC
Borges
André
A
Mendes
Gustavo D
GD
De Nucci
Gilberto
G
D000328:Adult; D000638:Amiodarone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D018592:Cross-Over Studies; D005260:Female; D005502:Food; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization; D013607:Tablets; D053719:Tandem Mass Spectrometry
D000889:Anti-Arrhythmia Agents; D013607:Tablets; D000638:Amiodarone