Pharmacological propertiesPharmacodynamic propertiesThiamazole interferes dose-dependently with the incorporation of iodine into tyrosine and with the new synthesis of thyroid hormones. This allows symptomatic therapy of hyperthyroidism regardless of its cause. The release of previously synthesized thyroid hormones from the thyroid is not affected. Pharmacokinetic properties Thiamazole is almost completely absorbed after oral administration. Maximum serum concentrations are reached within 0.4 - 1.2 hours. Pharmacokinetics of thiamazole can be described by a one-compartment model with a half-life of approx. 3 hours. The half-life is prolonged in case of hepatic insufficiency. Thiamazole is accumulated in the thyroid where it is metabolized slowly. This leads to a duration of action of almost 24 hours for the single dose. The thiamazole levels in serum do therefore not reflect its therapeutic effectiveness. The pharmacokinetics of thiamazole is not measurably influenced by disturbances in thyroid function. Thiamazole is eliminated via the kidneys and the bile; only 7 - 12 % are excreted in unchanged form, the remainder in the form of metabolites. Thiamazole is rapidly and completely absorbed and undergoes practically no protein binding. The maximum serum concentrations are reached after 0.4 - 1.2 hours. Preclinical safety data Acute toxicity: In mice the LD50 after oral administration is about 800 mg/kg of bodyweight, in rats the LD50 after oral administration is 1250 mg/kg of bodyweight. Chronic toxicity: See point 4.8. undesirable effects.- Mutagenicity: No information is available on mutagenicity. So far no indications of any kind have become known suggesting damage to the progeny due to damages in the genous caused by thiamazole. Cancerogenicity: No long-term animal studies on carcinogenicity have been carried out with thiamazole. |
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