Comparative bioavailability study with two amiodarone tablet formulations in healthy subjects

Abstract

The aim was to assess the comparative bioavailability of two formulations (200 mg tablet) of amiodarone in healthy volunteers. METHODS: This Open label, Randomized, One period, Two Treatment, One Sequence, Parallel Design study was conducted in 36 healthy Indian adult volunteers. Subjects received amiodarone 2 x 200 mg of either test or reference formulation. After study drug administration, serial blood samples were collected over a period of 96 hours. The samples were analyzed for amiodarone by a pre-validated HPLC method. Pharmacokinetic (PK) parameters C_max, T_max, t_1/2, AUC_0-t, AUC _0-∞, and k_el, were determined for the 2 amiodarone formulations. C_max, AUC_0-t, and AUC_0-∞ were used to test for bioequivalence after log-transformation of plasma data. The formulations were to be considered bioequivalent if the log-transformed ratios of C_max, AUC_0-t, and AUC_0-∞ were within the predetermined bioequivalence range of 80% to 125%. A total of 36 healthy subjects were enrolled. No significant differences were found based on analysis of variance, with mean values and 90% confidence intervals of test/reference ratios for these parameters as follows: C_max, 303.68 versus 289.43 ng/mL (87.46 - 122.18); AUC_0-t, 3811.26 versus 3806.08 ng.hr/mL (82.87 - 118.79); and AUC_0-∞, 4787.95 versus 4800.96 ng.hr/mL (82.79 - 117.82). In these healthy Indian volunteers, results from the PK analysis suggested that the test and reference formulations of amiodarone 200 mg tablets were bioequivalent. Both the formulations were well tolerated.