Effects of Chronic Administration of Amiodarone on Kinetics of Metabolism of Iodothyronines*

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Abstract
Treatment with amiodarone, an iodinated antiarrhythmic drug, is associated with increases in serum rT3 [reverse triiodothyronine] and serum L-T4 [thyroxine] with a mild variable decrease in T3. The metabolic basis for these changes was examined by studying the kinetics of metabolism of 125I-labeled iodothyronines in rabbits given amiodarone (20 mg/kg BW [body wt]) for 3 wk. The mean .+-. SE MCR [metabolic clearance rate] of rT3 was significantly (P < 0.05) lower in amiodarone treated rabbits (1.88 .+-. 0.14 l/day) than that in the control animals (2.72 .+-. 0.25 l/day), with no appreciable changes in the MCR of T3. The mean MCR of T4 was also significantly lower in amiodarone-treated animals than in controls (0.23 .+-. 0.03 vs. 0.37 .+-. 0.04 l/day; P < 0.05). amiodarone had no significant effect on daily production rates (PR) of rT3 or T3, but the PR of T4 showed an increase which was significant (P < 0.05) when expressed per unit BW. The mean .+-. SE molar ratio of daily PR of T3 and T4 was reduced significantly (P < 0.05) from 0.75 .+-. 0.12 in controls to 0.35 .+-. 0.06 in drug-treated rabbits. Amiodarone treatment was also associated with a moderate reduction in the ratio of the PR of rT3 and T4, but the change was not statistically significant. Amiodarone administration apparently is associated with a reduction in the MCR or rT3 and T4 and a reduction in monodeiodination of T4 in the outer ring; monodeiodination of T4 in the inner ring either remains unaffected or decreases moderately.