Euthyrox Mechanism of Action

Thyroid Hormone Replacement.
Pharmacology: Pharmacodynamics: Levothyroxine, the active ingredient in Euthyrox, is a synthetic thyroid hormone, which is identical to the natural thyroid hormone thyroxine (T4). The human organism does not differentiate between natural T4 hormone and synthetic levothyroxine because of their identical effects.
Levothyroxine is converted to tri-iodo-thyronine (T3) in the peripheral organs and develops its specific effect at the T3-receptor.
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 hemodialysis nor hemoperfusion.
The half-life of levothyroxine is on average 7 days. In hyperthyroidism, it is shorter (3-4 days) and in hypothyroidism, it is longer (approximately 9-10 days).
The volume of distribution amounts to about 10-12 L. The liver contains 1/3 of the entire extrathyroidal 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 feces. 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. In incidents of poisoning (attempts at suicide) in humans, doses of 10 mg levothyroxine were tolerated without complications. In general, serious complications, such as threat to vital functions (respiration and circulation) need not be expected unless coronary heart disease is present.
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. No substantial adverse reactions occurred in dogs. Several cases of sudden cardiac death have been reported in patients with long years of levothyroxine abuse.
Reproduction Toxicity: Thyroid hormones pass the placenta only in slight, ineffective amounts. Ample experience in humans is available on therapy with levothyroxine in all phases of pregnancy: there is no evidence of any toxic effect on the fetuses or of drug-induced malformations.
No information is available on harmful effects on male or female fertility.
There have been no indications of any kind in this connection.
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.