The Thyroid Accumulation, Oxidation and Metabolic Fate of35S—Methimazole in the Rat

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Abstract
35S—Methimazole (MMI) was given ip to rats and the tissue distribution of radioactivity, thyroid metabolism and excretion studied over a period of 4 days. An accumulation of radioactivity and of unmetabolised methimazole was found in the thyroid, whereas the radioactivity disappeared rapidly in all other tissues studied. A tissue/plasma (T/P) ratio of radioactivity of 88.6 was demonstrated in the thyroid 12 hr after administration of a single dose of 35S—MMI with a T/P ratio of 2.1 and 1.7 in kidney and liver, respectively. All other tissues had a T/P ratio of less than one. TLC and liquid scintillation analysis of plasma and of thyroid homogenates showed a T/P ratio for 35S—MMI of 2.0 at 1 hr after the dose, rising to 25.5 after 8 hr. The methimazole was mainly oxidised to sulphate in the thyroid. TLC of plasma showed the presence of three compounds; methimazole, sulphate and protein bound radioactivity. Most of the radioactivity was excreted by the kidneys (the majority in the first 24 hr) with only 7.9% of the dose present in the feces. Six radioactive compounds were found in the urine: methimazole, sulphate, a highly polar compound, and three minor unknown compounds.(Endocrinology91: 747, 1972)

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