Effects of chronic administration of amiodarone on kinetics of metabolism of iodothyronines.

Treatment with amiodarone, an iodinated anti-arrhythmic drug, is associated with increases in serum rT3 and serum L-T4 with a mild variable decrease in T3. We have examined the metabolic basis for these changes by studying the kinetics of metabolism of 125I-labeled iodothyronines in rabbits given amiodarone (20 mg/kg BW) for 3 weeks. The mean +/- SE MCR of rT3 was significantly (P less than 0.05) lower in amiodarone-treated rabbits (1.88 +/- 0.14 liters/day) than that in the control animals (2.72 +/- 0.25 liters/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 liters/day; P less than 0.05). Amiodarone had no significant effect on daily production rates (PRs) of rT3 or T3, but the PR of T4 showed an increase which was significant (P less than 0.05) when expressed per unit BW. The mean +/- SE molar ratio of daily PRs of T3 and T4 was reduced significantly (P less than 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 PRs of rT3 and T4, but the change was not statistically significant. The overall data suggest that amiodarone administration is associated with a reduction in the MCRs of 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.