Source: Health Products Regulatory Authority (IE) Revision Year: 2021 Publisher: PRO.MED.CS Praha a.s., Telcska 377/1, Praha 4, Michle, 14000, Czech Republic
Pharmacotherapeutic group: bile and liver therapy; bile acid preparations
ATC code: A05AA02
Ursodeoxycholic acid is found in small amounts in human gall.
Upon oral administration, it induces a decline in cholesterol saturation of the gall bladder through blocking of cholesterol resorption in the intestine and decline in cholesterol secretion to the gall. A gradual decomposition of cholesterol gallstones is presumably achieved through dispersion of cholesterol and forming of liquid crystals.
The effect of ursodeoxycholic acid in liver and cholestatic diseases is, according to current knowledge, based on relative exchange of lipophilic, detergent-type, toxic bile acids for hydrophilic, cytoprotective, non-toxic ursodeoxycholic acid, improvement of the secretory performance of liver cells and immunoregulative processes.
From clinical reports long-term experience up to 10 years and more is available with UDCA treatment in paediatric patients suffering from cystic fibrosis associated hepatobiliary disorders (CFAHD). There is evidence that treatment with UDCA can decrease bile duct proliferation, halt progression of histological damage and even reverse hepatobiliary changes if given at early stage of CFAHD. Treatment with UDCA should be started as soon as the diagnosis of CFAHD is made in order to optimise treatment effectiveness.
Orally administered ursodeoxycholic acid is resorbed fast in the jejunum and upper ileum through passive, and in terminal ileum active transport. The resorption rate generally amounts to 60–80%. Upon resorption the bile acid conjugates almost completely with the glycine and taurine amino acids in the liver and then biliary excretion follows. The first-pass-clearance through liver amounts up to 60%.
Depending on the daily dose and the underlying disease or the liver condition, the more hydrophilic ursodeoxycholic acid accumulates in the gall. Concurrently, a relative reduction of the other, more lipophilic bile acids takes place. In the intestine, a partial bacterial degradation to 7-keto-lithocholic acid and lithocholic acid takes place. The lithocholic acid is liver-toxic and induces liver parenchymal damage in a range of animal species. In humans, it is resorbed only to a very minor extent. This fraction is sulphated by the liver and thus detoxicated and then, again, biliary and subsequently fecal excretion follow.
The biological half-life of ursodeoxycholic acid is around 3.5 to 5.8 days.
Studies conducted on animals concerning acute toxicity did not indicate any toxic damage.
Subchronic toxicity studies in monkeys showed hepatotoxic effects in the groups given high doses, including functional changes (e.g. liver enzyme changes) and morphological changes such as bile duct proliferation, portal inflammatory foci and hepatocellular necrosis. These toxic effects are most likely attributable to lithocholic 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.
Long-term studies in mice and rats revealed no evidence of ursodeoxycholic acid having carcinogenic potential. In vitro and in vivo genetic toxicology tests with ursodeoxycholic acid were negative.
In studies in rats, tail aplasias occurred after a dose of 2,000 mg of ursodeoxycholic acid per kg of body weight. In rabbits, no teratogenic effects were found, although there were embryotoxic effects (from a dose of 100 mg per kg of body weight). Ursodeoxycholic acid had no effect on fertility in rats and did not affect peri-/postnatal development of the offspring.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
