Pharmacotherapeutic group: Thyroid hormones. ATC-Code: H03A A01.
Pharmacology: Pharmacodynamics: The synthetic levothyroxine contained in Euthyrox is identical in effect with the naturally occurring major hormone secreted by the thyroid. It is converted to T3 in peripheral organs and, like the endogenous hormone, develops its specific effects at the T3 receptors. The body is not able to differentiate between endogenous and exogenous levothyroxine.
Pharmacokinetics: Orally given levothyroxine is absorbed almost exclusively in the upper small intestine. Depending on the galenical formulation absorption amounts up to 80% tmax is approximately 5 to 6 hours.
Following oral administration the onset of action is seen after 3-5 days. Levothyroxine exhibits an extremely high binding to specific transport proteins of about 99.97%.
This protein hormone binding is not covalent and so the bound hormone in plasma is in continuous and very rapid exchange with the fraction of the free hormone.
Due to its high protein binding levothyroxine undergoes neither haemodialysis nor haemoperfusion.
The half-life of levothyroxine is on average 7 days. In hyperthyroidism it is shorter (3-4 days) and in hypothyroidism it is longer (approx. 9-10 days). The volume of distribution amounts to about 10-12 l. The liver contains 1/3 of the entire extra-thyroidal levothyroxine, which is rapidly exchangeable with the levothyroxine in serum. Thyroid hormones are metabolized mainly in the liver, kidneys, brain and muscles. The metabolites are excreted with urine and faeces. The overall metabolic clearance for levothyroxine is about 1.2 l plasma/day.
Toxicology: Preclinical safety data: Acute toxicity: Levothyroxine has a very slight acute toxicity.
Chronic toxicity: The chronic toxicity of levothyroxine was studied in various animal species (rat, dog). At high doses, signs of hepatopathy, increased occurrence of spontaneous nephroses as well as changes in organ weights were observed in rats.
Reproduction toxicity: Reproductive toxicity studies in animals have not been performed.
Mutagenicity: No information is available on this subject. So far no indications of any kind have become known suggesting damage to the progeny due to changes in the genome caused by thyroid hormones.
Carcinogenicity: No long-term animal studies have been carried out with levothyroxine.