Dilantin and Salicylate Effects on Hepatic Thyroxine Bio-Availability and Dialyzable Thyroxine

Summary

Earlier studies have shown that drugs such as dilantin inhibit T₄ binding by thyroid hormone binding globulin (TBG) and cause a displacement of T₄ from TBG to prealbumin with no change in the albumin-bound T₄ fraction. Since recent studies have shown albumin-bound T₄ is freely transported into liver, the present studies are designed to investigate drug effects on T₄ transport in liver.

The effect of salicylate and diphenylhydantoin (Dilantin) on T₄ in human serum were examined both in vitro by using equilibrium dialysis and in vivo in the rat liver by using a tissue sampling single injection technique. Serum was obtained from 6 healthy normal volunteers and was made either 0 or 0.5 mM Dilantin and either 0 or 10 mM sodium salicylate. The portal vein injection vehicle contained ¹²⁵I-T₄/³H-water (highly diffusible internal reference) mixed with either a) Ringer's (0.1 g/dl albumin), b) 5% T₄ antiserum, or c) 80% human serum.

The free dialyzable fraction in vitro was raised by 40 and 125% after the addition of Dilantin and salicylate respectively. However, the percent of total T₄ that was transported into liver on one pass, 17 ± 1%, was not different in the control, the salicylate treated, or the Dilantin-treated sera. Therefore, in contrast to the in vitro dialyzable measurement of free T₄, which is elevated by toxic concentrations of Dilantin or salicylate, the bio-available fraction of T₄ as determined by the single pass perfusion technique, is unchanged in rat liver in vivo. These drug-induced changes in free T₄ in vitro and bio-available T₄ in vivo are similar to the ones reported previously in non-thyroidal illness.

Key words

Dilantin - Salicylates - Thyroxine