DIFFERENT EFFECTS OF AMIODARONE ON TRANSPORT OF T-4 AND T-3 INTO THE PERFUSED-RAT-LIVER

Uptake and metabolism of thyroxine (T-4) and 3,5,3'-triiodothyronine (T-3) 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 (t(1/2)) of the fast component of the biphasic thyroid hormone disappearance from the medium and by the fractional influx rate constant (k(21)). Metabolism was assessed by the t(1/2) 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 T-4 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 T-3 were unaffected by amiodarone. The results showed that the different transport systems for T-4 and T-3 described in isolated rat hepatocytes may also be operative in the intact rat liver. Furthermore, it can be concluded that the low-T-3 syndrome, caused by treatment with amiodarone, may be due to both impaired transport and impaired 5'-deiodination.