Ursodeoxycholic acid

Ursodeoxycholic acid (INN, BAN and AAN), also known as ursodiol (USAN) and the abbreviation UDCA, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria.

Endogenous effects
Primary bile acids are produced by the liver and stored in the gall bladder. When secreted into the intestine, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat (cholesterol) gallstones non-surgically.

While some bile acids are known to be colon tumor promoters (e.g. deoxycholic acid), others such as ursodeoxycholic acid are thought to be chemopreventive, perhaps by inducing cellular differentiation and/or cellular senescence in colon epithelial cells.

It is believed to inhibit apoptosis.

Ursodeoxycholic acid has also been shown experimentally to suppress immune response such as immune cell phagocytosis. Prolonged exposure and/or increased quantities of systemic (throughout the body, not just in the digestive system) ursodeoxycholic acid can be toxic.

Medical uses
A Cochrane review looking at primary biliary cirrhosis found that although ursodeoxycholic acid showed a reduction in liver biochemistry, jaundice, and ascites, it did not decrease mortality or liver transplantation. Ursodiol is the only FDA approved drug to treat primary biliary cirrhosis.

Ursodiol may be used for biliary stasis in pregnant women to relieve the symptoms of itching and decrease bile absorption.

In absence of biochemical response to ursodeoxycholic acid, its use is associated with an incidence of 20% hepatocellular carcinoma in those with primary biliary cirrhosis in 15 years.

In children, its use is not licensed, as its safety and effectiveness are not established. In double the recommended daily dose ursodeoxycholic acid reduces elevated liver enzyme levels in those with primary sclerosing cholangitis, but its use was associated with an increased risk of serious adverse events (the development of cirrhosis, varices, death or liver transplantation) in patients who received ursodeoxycholic acid compared with those who received placebo). The risk was 2.1 times greater for death, transplantation, or minimal listing criteria in patients on ursodeoxycholic acid than for those on placebo. Serious adverse events, were more common in the ursodeoxycholic acid group than the placebo group.

Mechanism of action
The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery. The drug is very expensive, however, and if the patient stops taking it, the gallstones tend to recur if the condition that gave rise to their formation does not change. For these reasons, it has not supplanted surgical treatment by cholecystectomy.

Trade names
Ursodeoxycholic acid can be chemically synthesized and is marketed under multiple trade names, including Actigall, BILIVER, Coric, Deursil, Egyurso, Udiliv, UDOXYL, Urso, Urso Forte, Ursocol, Ursofalk, and Ursosan.

Production
The drug is generally not derived from animals. However, it is believed up to 10,000 bile bears are kept on farms in China, Vietnam and South Korea for the purpose of harvesting ursodeoxycholic acid. Ursodeoxycholic acid is found in large quantities in bear bile.