Amiodarone does not affect the distribution and fractional turnover of triiodothyronine from the plasma pool, but only its generation from thyroxine in extrathyroidal tissues.
The peripheral metabolism of T3 has been studied in 10 hypothyroid patients receiving daily oral replacement doses of 200 micrograms T4 or 60 micrograms T3, in divided doses, before and during treatment with 400 mg amiodarone (AMD) daily for 3 weeks. Each patient received 1 microCi/kg BW [125I]T3, iv. Blood samples were drawn at 10, 20, 30, and 60 min and 2, 4, 6, 8, 12, 24, 36, 48, 60, and 72 h, followed by trichloroacetic acid precipitation and ethanol extraction of the serum samples. The parameters of T3 kinetics were obtained from the area under the disappearance curve of [125I]T3 from serum using a noncompartmental analysis. In five T4-treated patients, AMD induced a significant increase in serum T4 (P less than 0.02), serum free T4 (P less than 0.01), and serum TSH (P less than 0.02) and a marked decrease in serum T3 (P less than 0.005). Fractional turnover and MCRs were not affected by the drug. However, the extrathyroidal pool of T3 (P less than 0.02) and its degradation rate (P less than 0.001) were both significantly diminished. In the five T3-treated patients, AMD did not induce alterations in the parameters of T3 kinetics or in serum T3 and TSH concentrations. The data clearly establish that AMD does not affect the distribution and fractional removal of T3 from the plasma pool, but only its generation from T4 in extrathyroidal tissues. This conclusion does not rule out the possibility that the drug may interfere with a number of intracellular events dependent on T3 action which may be independent of T3 deiodination.
Zaninovich
A A
AA
CONICET, Center of Nuclear Medicine, Hospital de Clínicas, University of Buenos Aires, Argentina.
Bosco
S C
SC
Fernandez-Pol
A J
AJ
D000328:Adult; D000638:Amiodarone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013974:Thyroxine / Q000378:metabolism* / Q000627:therapeutic use; D014284:Triiodothyronine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D014284:Triiodothyronine; D000638:Amiodarone; D013974:Thyroxine