Studies on the Thyroxine-Diphenylhydantoin Interaction:Effect of 5,5′-Diphenylhydantoin on the Displacement of L-Thyroxine from Thyroxine-Binding Globulin (TBG)

5,5′-Diphenylhydantoin added to serum causes a fall in the quantity of I131 L-thyroxine associated with thyroxine-binding globulin and a reciprocal increase in the amount associated with prealbumin and albumin, as determined by conventional paper electrophoresis in a glycine acetate buffer at pH 8.6. The addition of an excess of stable L-thyroxine appears to abolish this effect. 5,5′-Diphenylhydantoin-4-C-14, however, migrates to the albumin-prealbumin area in this electrophoretic system and not to the alpha globulin region. In an incubating system of red cells and serum, diphenylhydantoin increases the red cell uptake of I131 L-thyroxine. Also, diphenylhydantoin accelerates the dialysis of I131 L-thyroxine across a semipermeable membrane, from a compartment of diluted serum to a surrounding compartment of an aqueous phosphate buffer at pH 7.4. These findings suggest that diphenylhydantoin displaces thyroxine from the thyroxinebinding globulin, raises the level of “free” thyroxine, and effects a redistribution of thyroxine among other species of serum and cellular binding sites.