Bioavailability of Amiodarone tablets administered with and without food in healthy subjects

The tablet form of amiodarone is indicated for the treatment of recurrent v entricular fibrillation or hemodynamically unstable ventricular tachycardia . It is recommended that the tablet be token with meals in cases of gastroi ntestinal intolerance. However, the effect of food on its bioavailability i s unknown. The primary objective of this study was to determine the effect of food on the bioavailability of amiodarone. This was a 2-period crossover study conducted in 30 healthy mole subjects, Subjects were randomly assign ed to 1 of 2 sequences in which the following 2 treatments were administere d: (1) a single-dose of amiodarone (three 200-mg Cordarone tablets) after a n overnight fast, and (2) the same dose immediately after a standard high-f at breakfast, plasma concentrations of amiodarone and desethylamiodarone (D EA) were measured for 6 weeks after each dose. Food enhanced the extent of absorption, resulting in a peak concentration (C-max) and area under the cu rve (AUC(T)) 3.8 and 2.4 times the respective values under fasting conditio ns. Food also significantly increased the rate of absorption, reducing the time (t(max)) to C-max from 7.1 to 4.5 hours. The effect of food on DEA lev els was significant but less pronounced. An in vitro dissolution study conf irmed a marked difference between amiodarone release under simulated fed an d fasting conditions. Thus, food significantly enhances both the rate and e xtent of absorption of amiodarone, which is attributed partially to the eff ect of food on drug release from its formulation. Therefore, it is recommen ded that amiodorone tablets be taken consistently with meals. (C) 2001 by E xcerpta Medica, Inc.