The correlation of serum amiodarone levels with abnormalities in the metabolism of thyroxine

Abstract

Amiodarone, a widely used iodine-containing antiarrhythmic drug, has been shown to divert the peripheral metabolism of T4 towards rT3 than T3. In this prospective study we correlated the concentration of the peripheral thyroid hormones in serum with that of amiodarone. Fifteen euthyroid volunteers were studied, 5 men and 10 women, with a mean age of 64.2 yr, who suffered from various cardiac arrhythmias (atrial fibrillation or multiple ventricular extrasystoles). Serum amiodarone, T4, T3, rT3 and TSH were determined before and 3, 7, and 14 days after the administration of 400-600 mg amiodarone/day. There was a small increase in serum T4 and a suggestive decrease in serum T3. The increase in serum rT3 was significant, with p less than 0.05 for 3 days, p less than 0.01 for 7 days and p less than 0.005 for 14 days. There was a significant correlation between the level of serum amiodarone and the rise in serum rT3 (r = 0.385, p less than 0.05). The rise in rT3 is the main thyroid abnormality after amiodarone administration and may be used as a rough index of the serum concentration of this drug.

Inhibition of purified pig and human liver retinyl ester hydrolase by pharmacologic agents

“…To evaluate whether the drug concentration used in these experiments and the calculated IC 50 values were comparable with the serum and tissue concentrations seen after therapeutic dosage, we compiled data for the test compounds from a review of the available literature ( Table 2; Refs. [13][14][15][16][17][18][19][20][21][22]. For all drugs, except two, for which data could be compared, their expected clinical serum concentration was below their IC 50 values for hepatic REH inhibition.…”

“…Amiodarone could also inhibit enzymic activity by a direct interaction with the polypeptide chain at the interface or by modifications of surface charge, as amiodarone is an ionized amine at pH 7.4 (37). Moreover, amiodarone has a very long half-life (38) and extensive distribution to the liver and other organs, reaching tissue concentrations up to 11-fold higher than in plasma ( Comparison of the concentration of tested drugs in serum and liver (assuming that 1 g of tissue approximates 1 mL in volume) as adapted from the literature (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Abbreviation: DNA, data not available; for other abbreviation see Table 1.…”

Therapeutic monitoring of amiodarone and desethylamiodarone after surgical ablation of atrial fibrillation-evaluation of the relationship between clinical effect and the serum concentration

“…Other authors had previously also reported the same finding ( Lafuente-Lafuente et al, 2009 ). In terms of influence on thyroid function, only Anastasiou-Nana et al described a significant correlation between the AMI serum level and the rise of the rT3 serum level ( Anastasiou-Nana et al, 1984 ). The effect of DEA was not examined in this study.…”

The effect of iodide on serum thyroid hormone levels in normal persons, in hyperthyroid patients, and in hypothyroid patients on thyroxine replacement*

“…There was indeed a small increase in serum T4, significant at days 1 and 14, together with a small but significant decrease in serum TSH at day 1. These mild alterations, without significant changes in serum T3 and rT3, are in no way comparable to the striking shift of the peripheral metabolism of T4 towards rT3 rather than T3 which is observed after the administration of amiodarone (Pritchard et al, 1975;Burger et al, 1976;Jonckheer et ul., 1978;Melmed et al, 1981;Anastasiou-Nana et al, 1984), benziodarone (Xanthopoulos et al, 1986) and other iodinated substances (Burgi et al, 1976;Sing-Yung et al, 1978). This was despite the fact that the dose of iodine used in this study was comparable to that contained in amiodarone and benziodarone.…”