Ursodeoxycholic Acid: Definition, Medical Uses, Mechanism of Action, Side Effects, Pharmacodynamics, Route of Elimination and Toxicity

It is also known as ursodiol and the abbreviation UDCA; it is a secondary bile acid.

Ursodeoxycholic acid (INN, BAN, and AAN), and the abbreviation UDCA, from the Latin name Ursus which means bear, since bear bile contains the substance, is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria.

Problems with the consistency of bile (thickening) and the way it flows cause liver disease in up to 20% of young people with cystic fibrosis. The bile ducts can become blocked and cause cirrhosis in one or more liver parts.

It is a naturally-occurring bile acid and is used to dissolve gallstones that are rich in cholesterol. It is also used to improve bile flow in primary biliary cirrhosis.

Endogenous effects

Primary bile acids are produced by the liver and stored in the gallbladder.

When secreted in the intestine, primary bile acids can be metabolized to secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats.

Ursodeoxycholic acid helps regulate cholesterol by slowing the intestine’s absorption of cholesterol molecules while breaking down cholesterol-containing micelles.


Due to this property, ursodeoxycholic acid treats gallstones (cholesterol) without surgery. It is also used to relieve itching during pregnancy in some women with obstetric cholestasis.

While some bile acids are known to promote colon tumors (e.g., deoxycholic acid), others, such as ursodeoxycholic acid, are believed to be chemopreventive, perhaps inducing cell differentiation and cell senescence in epithelial cells. Colon.

It is believed to inhibit apoptosis. Ursodeoxycholic acid has also been shown to suppress immune responses, such as phagocytosis of immune cells.

Prolonged exposure and increased amounts of systemic ursodeoxycholic acid (throughout the body, not just the digestive system) can be toxic.

Medical uses

Ursodeoxycholic acid is a naturally-occurring bile acid taken as a tablet or liquid to prevent liver disease in people with cystic fibrosis.

Ursodeoxycholic acid improves measures of liver function, reduces the risk of developing chronic liver disease, and improves overall outcomes in people with cystic fibrosis.

An incomplete list of current uses is as follows:

Reduction of gallstone formation, either in patients with gallstones not suitable for cholecystectomy or obese patients who experience rapid weight loss to prevent gallstone formation.

For the treatment of primary biliary cholangitis (also known as primary biliary cirrhosis, PBC). To improve bile flow in patients with cystic fibrosis (controversial). In newborns with biliary insufficiency.

After bariatric surgery, to prevent cholelithiasis due to rapid weight loss with biliary cholesterol supersaturation and biliary dyskinesia secondary to cholecystokinin abnormalities and biliary enervation.

Meta-analyzes have yielded conflicting results on the mortality benefit of ursodeoxycholic acid in primary biliary cirrhosis; however, analyses excluding trials of short duration (i.e., <2 years) have shown a survival benefit generally considered more clinically relevant.

A Cochrane systematic review in 2012 found no significant benefit in reducing mortality, liver transplant rate, itching, or fatigue.

Ursodiol is the only drug approved by the Food and Drug Administration to treat primary biliary cirrhosis, but many patients do not respond; Other treatments are being studied.

Ursodiol can be used to treat intrahepatic cholestasis of pregnancy, relieve itching symptoms, decrease the infant mortality rate, and decrease bile absorption.

Ursodiol is not believed to reduce maternal mortality from bleeding in such cases.

In children, using ursodeoxycholic acid is not authorized since its safety and effectiveness have not been established. Evidence suggests that ursodeoxycholic acid is ineffective and unsafe in neonatal hepatitis and neonatal cholestasis.

There is insufficient evidence to justify the routine use of ursodeoxycholic acid in cystic fibrosis, especially from the data available to analyze long-term outcomes, such as death or the need for liver transplantation.

At twice the recommended daily dose, ursodeoxycholic acid reduces elevated liver enzyme levels in people with primary sclerosing cholangitis.

However, its use was associated with an increased risk of serious adverse events (the development of cirrhosis, varicose veins, death, or liver transplantation) in patients who received ursodeoxycholic acid compared to those who received placebo.

Serious adverse events were more common in the ursodeoxycholic acid group than placebo.

The risk was 2.1 times greater for death, transplantation, or minimum inclusion criteria in patients with ursodeoxycholic acid than those who received a placebo.

It is concluded that the use of ursodeoxycholic acid is associated with improved serum liver tests that are not always correlated with a better liver condition.

The WHO drug information advises against their use in primary sclerosing cholangitis at unapproved doses beyond 13 to 15 mg/kg/day.

Recent research at the University of Sheffield indicates that ursodeoxycholic acid shows promise in treating Alzheimer’s disease.

It was initially used to treat gallstones, but in recent years it has been used to treat and prevent the progression of cystic fibrosis-related liver disease.

Ursodeoxycholic acid will likely play a role in delaying the need for liver transplantation.

A placebo-controlled study of 145 patients with primary biliary cirrhosis found that the disease progressed more slowly in patients who received ursodeoxycholic acid.

This group also had a significantly lower chance of transplantation or death during the two-year study.

Mechanism of action

The drug reduces the absorption of cholesterol and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery.

If the patient stops taking the drug, gallstones tend to recur if the condition that led to their formation does not change. For these reasons, it has not supplanted surgical treatment by cholecystectomy.

Ursodeoxycholic acid has been shown to exert anti-inflammatory and protective effects on human epithelial cells in the gastrointestinal tract.

It has been related to regulating immunoregulatory responses by regulating cytokines, the defensins of antimicrobial peptides. It actively participates in the more excellent restoration of the wound in the colon.

Furthermore, the effects of ursodeoxycholic acid have been shown to exert actions outside of epithelial cells.


Ursodeoxycholic acid can be chemically synthesized and is marketed under multiple trade names, including Actibile, Actigall, Biliver, Deursil, Egyurso, Udcasid, Udiliv, Udoxyl, Urso, Urso Forte, Ursocol, Ursolalk, Ursosalk, Ursoserinox, You and Stener.

Side effects

Ursodeoxycholic acid has few known adverse effects. Diarrhea is an immediate adverse reaction. Patients may complain of an increase in itching when they start treatment.

This may respond to a reduction in the dose. Ursodeoxycholic acid is contraindicated if there is an acute gallbladder inflammation or a common bile duct obstruction.

  • Diarrhea .
  • Indigestion.
  • Headache.
  • Nausea or vomiting
  • Back pain.
  • Bloody and cloudy urine.
  • Black or tarry stools.
  • Unusual bleeding or bruising.
  • Frequent and painful urination.
  • Fever and cough
  • Hair loss.
  • Swelling of the eyelids, face, lips, and tongue.

In clinical trials with at least two years of follow-up, patients taking ursodeoxycholic acid had improved liver function tests. This cannot continuously improve the patient’s symptoms or liver histology.


Ursodiol (also known as ursodeoxycholic acid) is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. Primary bile acids are produced by the liver and stored in the gallbladder.

Intestinal bacteria can metabolize primary bile acids into secondary bile acids when secreted into the colon. Primary and secondary bile acids help the body digest fats.

Ursodeoxycholic acid helps regulate cholesterol by slowing the rate at which the intestine absorbs cholesterol molecules while breaking down cholesterol-containing micelles.

Due to this property, ursodeoxycholic acid is used to treat gallstones without surgery.

Ursodeoxycholic acid reduces elevated levels of liver enzymes by facilitating the flow of bile through the liver and protecting liver cells. The primary mechanism is antichollinic.

Although the exact process of ursodiol’s anticholnamic action is not fully understood, it is believed that the drug concentrates in the bile and lowers bile cholesterol by suppressing hepatic synthesis and cholesterol secretion and inhibiting its intestinal absorption.

The reduction of cholesterol saturation allows the gradual solubilization of cholesterol from gallstones, resulting in their final dissolution.

Route of elimination

Only small amounts of ursodiol appear in the systemic circulation, and tiny amounts are excreted in the urine.

Eighty percent of the lithocholic acid formed in the small intestine is excreted in the feces. However, the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to the relatively insoluble lithocholic conjugates that are excreted in the bile and are lost in the stool.


Accidental or intentional overdosage with ursodeoxycholic acid has not been reported. Ursodeoxycholic acid doses in the range of 16-20 mg/kg/day have been tolerated for 6-37 months without symptoms in 7 patients.

The LD50 for ursodeoxycholic acid in rats is more than 5000 mg/kg administered for 7-10 days and more than 7500 mg/kg for mice.

The most likely manifestation of a severe ursodeoxycholic acid overdose would probably be diarrhea, which should be treated symptomatically.