Pharmacological propertiesPharmacodynamic propertiesThe thyroid hormones contained in Novothyral are identical in effect with the naturally occurring hormones secreted by the thyroid gland. The characteristic thyroid effects on development, growth and metabolism are observed after partial conversion of levothyroxine to liothyronine, particularly in liver and kidney and after passage into the cells of the body. Pharmacokinetic properties Levothyroxine administered orally on an empty stomach is absorbed up to maximally 80 % predominantly from the small intestine in clear correlation with the type of the galenic preparation. Maximum plasma levels are attained about 6 hours after intake. Levothyroxine administered orally acts 3 - 5 days after start of an oral treatment. The distribution volume is about 1/2 liter/kg. Levothyroxine is bound to plasma proteins by more than 99 %. Metabolic clearance is about 1.2 liters of plasma/day. It is metabolized mainly in the liver, kidneys, muscles and brain. Liothyronine administered orally is absorbed up to 78 - 95 % predominantly form the small intestine. The maximum action after single administration of liothyronine is reached after 2 - 3 days. The higher metabolic clearance rate of about 15 liters of plasma/day can be explained by the plasma-protein bond which is slightly lower than that of levothyroxine. It is metabolized mainly in the liver, kidneys, muscles and brain. On account of their high protein bonds thyroid hormones only appear in slight quantities in hemodialysate. The bioavailability of levothyroxine sodium as Euthyrox 100 tablets, taken on an empty stomach, was determined to be 79.6 3 %. Liothyronine sodium is absorbed at a rate of 78 -95 %. 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 a threat to vital functions (respiration and circulation) need not be anticipated 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. After injection of small doses (up to 24 µg) of levothyroxine in chicken embryos the incidence of strophosomia was increased. 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. |
|
   |
|