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Arzneimittelforschung 2007; 57(9): 582-590
DOI: 10.1055/s-0031-1296653
Cardiac Drugs · Cardiac Stimulants · Coronary Drugs
Editio Cantor Verlag Aulendorf (Germany)

Comparative Bioavailability Study with Two Amiodarone Tablet Formulations Administered with and without Food in Healthy Subjects

Hilton Oliveira dos Santos Filho
2   Cartesius Analytical Unit , Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
2   Cartesius Analytical Unit , Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
,
Jaime O. Ilha
1   Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
2   Cartesius Analytical Unit , Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
,
Lara Cristina Silva
1   Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
,
André Borges
2   Cartesius Analytical Unit , Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
3   Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
,
Gustavo D. Mendes
1   Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
2   Cartesius Analytical Unit , Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
3   Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
,
Gilberto De Nucci
1   Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
2   Cartesius Analytical Unit , Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil
3   Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil
› Author Affiliations
Further Information

Publication History

Publication Date:
21 December 2011 (online)

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Abstract

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 chro-matography 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 pharmacoki-netic parameters were obtained, with and without food: AUClast, AUCinf, AU C0-240h, AUC0-72h and Cmax.

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 Cmax, 107.05 (95.88–119.51) and 100.2 (96.0–104.7) for AUClast, 107.27 (95.78–120.15) and 100.8 (97.0–104.8) for AUC0-72h , 106.76 (95.84– 118.94) and 100.2 (96.0–104.7) for AUC0-240h and AUCinf 105.15 (94.18–117.41) and 100.7 (96.6–105.0).

Conclusion: Since the 90 % CI for AUC0-72, and Cmax ratios were within the 80–125 % interval proposed by the US FDA, it was concluded that the amio-darone 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.

Key words

Amiodarone, bioavailability, effect of food on bioavailability, pharmacokinetics - Antiarrhythmics - CAS 19774-82-4