Ursodeoxycholic acid

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Ursodeoxycholic acid
300px
Ursodeoxycholic acid ball-and-stick.png
Systematic (IUPAC) name
3α,7β-dihydroxy-5β-cholan-24-oic acid
OR
(R)-4-((3R,5S,7S,8R,9S,10S,13R,14S,17R)-3,7-dihydroxy-
10,13-dimethylhexadecahydro-
1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid
Clinical data
Trade names Actigall
AHFS/Drugs.com monograph
MedlinePlus a699047
Licence data US Daily Med:link
Pregnancy
category
  • AU: B3
  • US: B (No risk in non-human studies)
Legal status
Routes of
administration		 oral
Identifiers
CAS Number 128-13-2 YesY
ATC code A05AA02 (WHO)
PubChem CID: 31401
IUPHAR/BPS 7104
DrugBank DB01586 YesY
ChemSpider 29131 YesY
UNII 724L30Y2QR YesY
KEGG D00734 YesY
ChEBI CHEBI:9907 YesY
ChEMBL CHEMBL1551 YesY
Synonyms ursodeoxycholic acid, Actigall, Ursosan, Urso, Urso Forte
PDB ligand ID IU5 (PDBe, RCSB PDB)
Chemical data
Formula C24H40O4
Molecular mass 392.56 g/mol
  • O=C(O)CC[C@H]([C@H]1CC[C@@H]2[C@]1(C)CC[C@H]4[C@H]2[C@@H](O)C[C@@H]3C[C@H](O)CC[C@@]34C)C
  • InChI=1S/C24H40O4/c1-14(4-7-21(27)28)17-5-6-18-22-19(9-11-24(17,18)3)23(2)10-8-16(25)12-15(23)13-20(22)26/h14-20,22,25-26H,4-13H2,1-3H3,(H,27,28)/t14-,15+,16-,17-,18+,19+,20+,22+,23+,24-/m1/s1 YesY
  • Key:RUDATBOHQWOJDD-UZVSRGJWSA-N YesY
Physical data
Melting point 203 °C (397 °F)
  (verify)

Ursodeoxycholic acid (INN, BAN and AAN), also known as ursodiol (USAN) and the abbreviation UDCA, from the root-word for bear urso, as bear bile contains the substance, 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. It is also used to relieve itching in pregnancy for some women who suffer obstetric cholestasis.

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.[1]

It is believed to inhibit apoptosis.[2]

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.[3]

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.[4] Ursodiol is the only FDA approved drug to treat primary biliary cirrhosis.[5]

Ursodiol may be used for biliary stasis in pregnant women to relieve the symptoms of itching and decrease bile absorption.[6]

In absence of biochemical response to ursodeoxycholic acid in PBC, its use is associated with an incidence of 20% hepatocellular carcinoma in 15 years.[7]

In children, ursodeoxycholic acid use is not licensed, as its safety and effectiveness have not been established. Evidence is accumulating that ursodeoxycholic acid is ineffective and unsafe in neonatal hepatitis and neonatal cholestasis.[8][9][10]

There is insufficient evidence to justify routine use of ursodeoxycholic acid in cystic fibrosis, especially that available data for analysis of long-term outcomes such as death or need for liver transplantation is lacking.[11]

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. Serious adverse events, were more common in the ursodeoxycholic acid group than the placebo group. The risk was 2.1 times greater for death, transplantation, or minimal listing criteria in patients on ursodeoxycholic acid than for those on placebo.[12]

It is concluded that ursodeoxycholic acid use is associated with improved serum liver tests that do not always correlate with improved liver disease status. WHO Drug Information advises against its use in primary sclerosing cholangitis in unapproved doses beyond 13–15 mg/kg/day.[13]

Mechanism of action

The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery. If the patient stops taking the drug the gallstones tend to recur if the condition that gave rise to their formation does not change.[14][15] For these reasons, it has not supplanted surgical treatment by cholecystectomy.

Also used to relieve itching in intrahepatic cholestasis of pregnancy (naltrexone may also be used).

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, Ursosan, Ursoserinox and Udimarin (India)

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Material Safety Data Sheet on Ursodiol MSDS. https://fscimage.fishersci.com/msds/70916.htm
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Urso package insert. Birmingham, AL: Axcan Pharma U.S.; 2000 Jan.http://www.axcan.com/pdf/urso_patient_brochure.pdf
  11. ↑ Cheng K, Ashby D, Smyth RL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst Rev. 2014 Dec 15;12:CD000222. doi:10.1002/14651858.CD000222.pub3 PubMed PMID 25501301.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ http://www.who.int/medicines/publications/druginformation/issues/26-1.pdf
  14. ↑ Public Assessment Report for paediatric studies submitted in accordance with Article 45 of Regulation (EC) No1901/2006, as amended http://www.google.com.eg/search?q=public+MAH+UDCA&hl=en-EG&gbv=2&oq=&gs_l=
  15. ↑ PUBLIC ASSESSMENT REPORT of the Medicines Evaluation Board in the Netherlands http://mri.medagencies.org/download/NL_H_2516_001_PAR.pdf

External links

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