Methimazole metabolite

When 20 mg/kg of methimazole was administered i.p. or orally to rats, urinary methimazole glucuronides accounted for 36-48% of the dose in 24 hours. The only other urinary metabolite accounted for 10-20% and was not characterized. An additional 14-20% of methimazole was excreted unchanged in 24 hour urine. The bile contained methimazole glucuronide and two unidentified metabolites. One of which was the same as the unidentified urinary metabolites. Plasma proteins bound 5% of methimazole which had no affinity for any specific tissue. Methimazole had a much greater CHCI3/H2O partition coefficient and 1 0 solubility than did propylthiouracil. Between 77 and 95% of the methimazole was excreted in the urine and approximately 10% in the bile. Since fecal excretion was neglegible an enter-ohepatic circulation was present. The half life of urinary excretion was 5-7 hours regardless of the route of administration (15). 

Propylthiouracil is rapidly but incompletely absorbed after oral administration. It is metabolized in the liver with an elimination half-life of 1-2 hours. Carbimazole is absorbed rapidly and converted to methimazole, the active metabolite. Methimazole is metabolized in the liver and excreted in urine, less than 10% as unmetabolized methimazole. The elimination half-life of methimazole varies from 5 to 15 hours. Clinical responses are seen in 10-20 days but 2-10 weeks are needed for maximal inhibition. 

These cases highlight a possible link between carbimazole, or its active metabolite methimazole, and congenital abnormalities, especially aplasia cutis and choanal atresia,... 

Extensive studies have been carried out on the metabolic fate of compounds (12) and (13) (36). After initial accumulation in the thyroid gland, the unchanged drugs and various metabolites appear in the urine. The carbethoxy group in carbimazole, which was introduced to mask the bitter taste of methimazole, is metabolically removed, and therefore carbimazole can be considered a prodrug of methimazole. 

Disposition in the Body. Rapidly and almost completely absorbed after oral administration and converted to the active metabolite methimazole. Almost completely excreted in the urine in 24 hours as metabolites 3-methyl-2-thiohydantoin has been identified as a minor metabolite in urine and plasma. About 3% of a dose is eliminated in the faeces. 

Carbimazole and methimazole (the chief metabolite of carbimazole) (t) 6h) and propylthiouracil (t) 2 h) are commonly used, but t) matters little since the drugs accumulate in the thyroid and act there for 30-40 h thus a single daily dose suffices. 

The half-life of propylthiouracil in plasma is about 75 minutes, whereas that of methimazole is 4 to 6 hours. The drugs are concentrated in the thyroid, and methimazole, derived from the metabolism of carbimazole, accumulates after carbimazole is administered. Drugs and metabolites appear largely in urine. 

Uses Treatment with the thionamides thia-mazole (carbimazole), its active metabolite methimazole, or propylthiouracil remains one of the main therapeutic methods in hyperthyroidism. Unlike treatment with or surgery, thionamides are not ablative and permanent remission rates are low, even after prolonged administration. Suppression of serum thyrotropin (TSH) when antithyroid drugs are discontinued is a poor prognostic indicator of cure [13 ]. In a retrospective study there were higher remission rates at 6,12, and 24 months after withdrawal of antithyroid drugs in 40 subjects who had mild hypothyroidism (serum TSH over 10 pIU/l) compared with 37 sex- and age-matched patients who remained euthyroid during treatment with... 

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