Rat heart thyroxine 5'-deiodinase is sensitively depressed by amiodarone.
Thyroxine 5'-deiodinase activity (5'-D) is depressed in rat liver by amiodarone. To investigate the possible tardive effect of amiodarone on 5'-D in different tissues, rats were fed amiodarone according to a short-term (group A, 50 mg amiodarone/kg/day for 10 days, total dose 150 mg, n = 16) and long-term regimen (group B, 25 mg amiodarone/kg/day for 20 days, n = 16) (control group, n = 12). Serum, heart, and other tissues were collected for 10 days after drug cessation. Thyroxine (T4), triiodothyronine (T3), amiodarone, and its active metabolite desethylamiodarone (DEA) were determined in serum, and 5'-D was determined in tissues. In group A, amiodarone concentrations in the heart at the time of drug cessation were two times higher than in group B. Higher amiodarone concentrations were also found in other tissues, and DEA was immeasurable in nearly all tissues at all times. In all tissues the amiodarone content declined rapidly. 5'-D was depressed to about 50% of controls (p less than 0.05) in heart throughout the 10-day observation period, despite unmeasureable drug levels (less than 0.03 microgram/g tissue). In contrast, liver and kidney 5'-D normalized after the first day in both treated groups, while muscle 5'-D did not differ from controls at any time. In conclusion, heart 5'-D seems to be more sensitively depressed by amiodarone than other tissues. Inhibition of thyroid hormone effect in the heart may contribute to the antiarrhythmic properties of amiodarone; however, it cannot be concluded that amiodarone is responsible for the tardive drug effect.
Gøtzsche
L S
LS
Second University Clinic of Internal Medicine, Kommunehospitalet, Aarhus, Denmark.
Boye
N
N
Laurberg
P
P
Andreasen
F
F
D000638:Amiodarone / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors*; D007457:Iodine Radioisotopes; D008099:Liver / Q000201:enzymology; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism
D007457:Iodine Radioisotopes; D009124:Muscle Proteins; D014284:Triiodothyronine; D007453:Iodide Peroxidase; D000638:Amiodarone; D013974:Thyroxine