[Relation between the dosage of methimazole and its intrathyroidal concentrations]

Intrathyroidal concentrations of methimazole (MMI) were measured by means of high-performance liquid chromatography in 46 patients with Graves' disease who had undergone thyroidectomy. In this experiment, the dose of the drug varied from 5 mg/day to 40 mg/day, and the interval between the last dose and surgery ranged from 2 to 26 hours, and the mode of drug administration varied from a single dose to four divided doses. With dose of MMI from 5 to 15 mg/day, intrathyroid levels of MMI increased with increasing dose, but without significant increase when the dose was above 15 mg/day. There was no difference between patients taking the drug in divided doses and those taking it in one single dose of the same amount, or between patients taking the final dose 2 hours before thyroid excision aud those taking it 26 hours before excision. Our results indicate a saturable uptake mechanism for MMI by the thyroid, and MMI 15 mg/day is the most satisfactory dose for treating hyperthyroidism. The intrathyroidal concentrations are maintained for 26 hours at least, and the single daily dose of MMI is effective and reasonable for treatment of Graves' disease.