Drug Competition for Thyroxine Binding to Transthyretin (Prealbumin): Comparison with Effects on Thyroxine-Binding Globulin*

We examined the effect of 26 drugs on T4 binding to transthyretin (TTR; prealbumin) and T4-binding globulin (TBG) by determining their ability to inhibit [125I]T4 binding to TTR isolated from normal human plasma and to serum diluted 1:10,000, respectively. The hierarchies for drug inhibition of T4 binding differed greatly for these two proteins. Relative to T4, the drugs were much more potent inhibitors of [125I]T4 binding to TTR than to TBG. Compounds of the anthranilic acid class, such as flufenamic, meclofenamic, and mefenamic acids, interacted particularly strongly with TTR. Flufenamic acid was more potent than T4 itself in inhibiting [125I]T4 binding [175 ± 17% (±sd); cf. T4; n = 3; P < 0.001], while mefenamic acid, diflunisal, and meclofenamic acid were 20–26% as potent as T4 in their interaction with TTR. The reactivity of diclofenac, fenclofenac, indomethacin, sulindac, and the diuretic ethacrynic acid was 0.8–2.1% relative to that of T4. In contrast, furosemide, the drug most highly reactive with...