Hypolipidernic, uricosuric, and thyroxine-displacing effects of MK-185 (halofenate)

MK-185, an ester structurally related to clofibrate, was given to hypertriglyceridemic patients for 6 week periods in a controlled double-blind crossover trial. Serum triglycerides decreased an average o f 50 per cent during the trial, but little change was noted in serum cholesterol. An average decrease of 30 per cent was noted in the serum uric acid, and 5 patients showed a uricosuric effect of the drug independent of the glomerular filtration rate. Plasma thyroxine (T₄) showed a significant increase while patients were taking MK-185. Further studies showed a decrease in protein-bound iodine and T₄ by column. An increase in the dialyzable fraction of T₄ in vivo suggested a thyroxine-displacing effect from thyroid-binding proteins. This hypothesis was confirmed by in vitro displacement by MK-185 free acid of ¹³¹I-labeled T₄ bound to thyroid-binding globulin.