Axialith Mechanism of Action

Pharmacotherapeutic group: Bile acid preparations. ATC Code: A05AA02 and A05B.
Pharmacology: Pharmacodynamics: Small amounts of ursodeoxycholic acid are found in human bile.
After oral administration, it reduces cholesterol saturation of the bile by inhibiting cholesterol absorption in the intestine and decreasing cholesterol secretion into the bile. Presumably as a result of dispersion of the cholesterol and formation of liquid crystals, a gradual dissolution of cholesterol gallstones occurs.
According to current knowledge, the effect of ursodeoxycholic acid in hepatic and cholestatic diseases is thought to be due to a relative exchange of lipophilic, detergent-like, toxic bile acids for the hydrophilic, cytoprotective, non-toxic ursodeoxycholic acid, to an improvement in the secretory capacity of the hepatocytes, and to immune-regulatory processes.
Pharmacokinetics: Orally administered ursodeoxycholic acid is rapidly absorbed in the jejunum and upper ileum through passive transport and in the terminal ileum through active transport. The rate of absorption is generally 60-80%. After absorption, the bile acid undergoes almost complete hepatic conjugation with the amino acids glycine and taurine and is then excreted with the bile. First-pass clearance through the liver is up to 60%.
Depending on the daily dose and underlying disorder or condition of the liver, the more hydrophilic ursodeoxycholic acid accumulates in the bile. At the same time, a relative decrease in other more hydrophilic bile acids is observed.
Under the influence of intestinal bacteria, there is a partial degradation to 7-keto-lithocolic acid ad lithocolic acid.
Lithocolic acid is hepatotoxic and causes liver parenchyma damage in a number of animal species. In human, only very small amounts are absorbed which are sulphated in the liver and thus detoxified, before excreted in the bile and ultimately in the faeces.
The biological half-life of ursodeoxycholic acid is 3.5-5.8 days.
Toxicology: Preclinical Safety Data: Acute toxicity: Acute toxicity studies in animals have not revealed any toxic damage.
Chronic toxicity: Subchronic toxicity studies in monkeys showed hepatotoxic effects in the groups given high doses, including functional changes (eg, liver enzyme changes) and morphological changes such as bile duct proliferation, port inflammatory foci and hepatocellular necrosis.
These toxic effects are most likely attributable to lithocolic acid, a metabolite of ursodeoxycholic acid, which in monkeys, unlike humans is not detoxified. Clinical experience confirms that the described hepatotoxic effects are of no apparent relevance in humans.
Mutagenic and tumorigenic potential: Long-term studies in mice and rats revealed no evidence of ursodeoxycholic acid having tumorigenic potential.
In vitro and in vivo genetic toxicology tests with ursodeoxycholic acid were negative.
Toxicity to reproduction: In studies in rats, tail malformation occurred after a dose of 2,000 mg ursodeoxycholic acid/kg body weight. In rabbits, no teratogenic effects were found, although there were embryotoxic effects (from a dose of 100 mg/kg body weight). Ursodeoxycholic acid had no effect on fertility in rats and did not affect perinatal/postnatal development of the offspring.