Different effects of amiodarone on transport of T4 and T3 into the perfused rat liver.
Uptake and metabolism of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were studied in isolated perfused livers of control and amiodarone-treated rats (40 mg.kg body wt-1.day-1, 22 days). With the use of this perfusion system and a two-pool model describing thyroid hormone kinetics, total uptake was evaluated by the half-time (t1/2) of the fast component of the biphasic thyroid hormone disappearance from the medium and by the fractional influx rate constant (k21). Metabolism was assessed by the t1/2 of the slow component, by determination of breakdown products in medium and bile, and by thyroid hormone disposal according to the two-pool model. Disposal was corrected for differences in mass transfer into the metabolizing pool. In amiodarone-treated rats, both uptake and metabolism of T4 were decreased. Furthermore, it was shown that only transport into the metabolizing liver compartment and not uptake into the nonmetabolizing liver compartment was decreased. Both uptake and total metabolism of T3 were unaffected by amiodarone. The results showed that the different transport systems for T4 and T3 described in isolated rat hepatocytes may also be operative in the intact rat liver. Furthermore, it can be concluded that the low-T3 syndrome, caused by treatment with amiodarone, may be due to both impaired transport and impaired 5'-deiodination.
de Jong
M
M
Department of Internal Medicine III, Medical Faculty, Erasmus University, Rotterdam, The Netherlands.
Docter
R
R
Van der Hoek
H
H
Krenning
E
E
Van der Heide
D
D
Quero
C
C
Plaisier
P
P
Vos
R
R
Hennemann
G
G
D000638:Amiodarone / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003470:Culture Media; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011441:Propylthiouracil / Q000494:pharmacology; D051381:Rats; D013974:Thyroxine / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D003470:Culture Media; D014284:Triiodothyronine; D011441:Propylthiouracil; D007453:Iodide Peroxidase; D000638:Amiodarone; D013974:Thyroxine