Editing Ursodeoxycholic acid

{{Short description|Medication and metabolite of cholesterol}}
{{Use dmy dates|date=February 2020}}
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{{Infobox drug
| verifiedrevid = 470620651
| image = Ursodeoxycholic acid acsv.svg
| width = 250
| alt               =
| image2 = Ursodeoxycholic acid ball-and-stick.png
| width2 = 250
| alt2              =
| caption           =

<!-- Clinical data -->
| pronounce         =
| tradename = Actigall, Urso, others
| Drugs.com = {{drugs.com|monograph|ursodiol}}
| MedlinePlus = a699047
| DailyMedID = Ursodiol
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Ursodiol, Heptiza 300/150 Use During Pregnancy | website=Drugs.com | date=4 November 2019 | url=https://www.drugs.com/pregnancy/ursodiol.html | access-date=20 February 2020}}</ref>
| pregnancy_category =
| routes_of_administration = [[Oral administration|By mouth]]
| class             =
| ATC_prefix = A05
| ATC_suffix = AA02
| ATC_supplemental =

<!-- Legal status -->
| legal_AU = S4
| legal_AU_comment = <ref>{{cite web | title=Prescription medicines: registration of new generic medicines and biosimilar medicines, 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-registration-new-generic-medicines-and-biosimilar-medicines-2017 | access-date=30 March 2024}}</ref>
| legal_BR =  <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = <ref>{{cite web | title=Product information | website=[[Health Canada]] | date=3 August 2000 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=11967 | access-date=3 March 2024}}</ref><ref>{{cite web | title=Details for: Ursodiol C | website=[[Health Canada]] | date=25 October 2021 | url=https://dhpp.hpfb-dgpsa.ca/dhpp/resource/100493 | access-date=3 March 2024}}</ref>
| legal_DE = <!-- Anlage I, II, III or Unscheduled-->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = POM
| legal_UK_comment = <ref>{{cite web | title=Ursodeoxycholic acid 300mg Tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=10 July 2019 | url=https://www.medicines.org.uk/emc/product/10064/smpc | access-date=29 April 2020}}</ref>
| legal_US = Rx-only
| legal_US_comment = <ref name="Actigall FDA label">{{cite web | title=Actigall (ursodiol, USP) capsules| website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ad414461-262f-43fe-9a3d-bab300b719ed | access-date=25 September 2021}}</ref><ref>{{cite web | title=Urso 250- ursodiol tablet, film coated Urso Forte- ursodiol tablet, film coated | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e8fc4fc2-fe5c-4cba-b6e0-5ceaf2157a61 | access-date=25 September 2021}}</ref>
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->
| legal_UN_comment =
| legal_status = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability   =
| protein_bound     =
| metabolism        =
| metabolites       =
| onset             =
| elimination_half-life =
| duration_of_action =
| excretion         =

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 128-13-2
| CAS_supplemental  =
| PubChem = 31401
| IUPHAR_ligand = 7104
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB01586
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 29131
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 724L30Y2QR
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00734
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 9907
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1551
| NIAID_ChemDB      =
| PDB_ligand = IU5
| synonyms = Ursodiol

<!-- Chemical and physical data -->
| IUPAC_name = 3α,7β-dihydroxy-5β-cholan-24-oic acid<br />OR<br />(''R'')-4-((3''R'',5''S'',7''S'',8''R'',9''S'',10''S'',13''R'',14''S'',17''R'')-3,7-dihydroxy-<br />10,13-dimethylhexadecahydro-<br />1''H''-cyclopenta[''a'']phenanthren-17-yl)pentanoic acid
| C=24 | H=40 | O=4
| SMILES = 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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChI_comment  =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RUDATBOHQWOJDD-UZVSRGJWSA-N
| density           =
| density_notes     =
| melting_point = 203
| melting_high      =
| melting_notes     =
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| sol_units         =
| specific_rotation =
}}

'''Ursodeoxycholic acid''' ('''UDCA'''), also known as '''ursodiol''', is a secondary [[bile acid]], produced in humans and most other species from metabolism by intestinal bacteria. It is synthesized in the liver in some species, and was first identified in [[bear bile|bile of bears]] of genus ''[[Ursus (mammal)|Ursus]]'', from which its name derived.<ref name="pmid8263415">{{cite journal | vauthors = Hagey LR, Crombie DL, Espinosa E, Carey MC, Igimi H, Hofmann AF | title = Ursodeoxycholic acid in the Ursidae: biliary bile acids of bears, pandas, and related carnivores | journal = Journal of Lipid Research | volume = 34 | issue = 11 | pages = 1911–1917 | date = November 1993 | pmid = 8263415 | doi = 10.1016/S0022-2275(20)35109-9 | doi-access = free }}</ref> In purified form, it has been used to treat or prevent several diseases of the [[liver]] or [[bile ducts]].

It is available as a [[generic medication]].<ref>{{cite web | title=2020 First Generic Drug Approvals | website=U.S. [[Food and Drug Administration]] (FDA) | date=23 February 2021 | url=https://www.fda.gov/drugs/first-generic-drug-approvals/2020-first-generic-drug-approvals | archive-url=https://web.archive.org/web/20210517140111/https://www.fda.gov/drugs/first-generic-drug-approvals/2020-first-generic-drug-approvals | url-status=dead | archive-date=17 May 2021 | access-date=25 September 2021}}</ref><ref>{{cite web | title=Ursodiol: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=205789 | access-date=25 September 2021}}</ref>

==Medical uses==
UDCA has been used as medical therapy in [[gallstone]] disease (cholelithiasis) and for [[biliary sludge]].<ref name="PMID2672842">{{cite journal | vauthors = Hofmann AF | title = Medical dissolution of gallstones by oral bile acid therapy | journal = American Journal of Surgery | volume = 158 | issue = 3 | pages = 198–204 | date = September 1989 | pmid = 2672842 | doi = 10.1016/0002-9610(89)90252-3 }}</ref><ref>{{cite journal | vauthors = Jüngst C, Kullak-Ublick GA, Jüngst D | title = Gallstone disease: Microlithiasis and sludge | journal = Best Practice & Research. Clinical Gastroenterology | volume = 20 | issue = 6 | pages = 1053–1062 | date = 2006 | pmid = 17127187 | doi = 10.1016/j.bpg.2006.03.007 }}</ref>  UDCA helps reduce the [[cholesterol]] saturation of bile and leads to gradual dissolution of cholesterol-rich gallstones.<ref name=PMID2672842/>

UDCA may be given after bariatric surgery to prevent cholelithiasis, which commonly occurs due to the rapid weight loss producing biliary cholesterol oversaturation and also biliary dyskinesia secondary to hormonal changes.<ref>{{cite journal | vauthors = Magouliotis DE, Tasiopoulou VS, Svokos AA, Svokos KA, Chatedaki C, Sioka E, Zacharoulis D | title = Ursodeoxycholic Acid in the Prevention of Gallstone Formation After Bariatric Surgery: an Updated Systematic Review and Meta-analysis | journal = Obesity Surgery | volume = 27 | issue = 11 | pages = 3021–3030 | date = November 2017 | pmid = 28889240 | doi = 10.1007/s11695-017-2924-y | s2cid = 4622165 }}</ref>

===Primary biliary cholangitis===
UDCA is used as therapy in [[primary biliary cholangitis]] (PBC; previously known as primary biliary cirrhosis) where it can produce an improvement in biomarkers.<ref>{{cite journal | vauthors = Poupon RE, Balkau B, Eschwège E, Poupon R | title = A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group | journal = The New England Journal of Medicine | volume = 324 | issue = 22 | pages = 1548–1554 | date = May 1991 | pmid = 1674105 | doi = 10.1056/NEJM199105303242204 | doi-access = free }}</ref> Meta-analyses have borne out conflicting results on the mortality benefit.<ref>{{cite journal | vauthors = Goulis J, Leandro G, Burroughs AK | title = Randomised controlled trials of ursodeoxycholic-acid therapy for primary biliary cirrhosis: a meta-analysis | journal = Lancet | volume = 354 | issue = 9184 | pages = 1053–1060 | date = September 1999 | pmid = 10509495 | doi = 10.1016/S0140-6736(98)11293-X | s2cid = 25562983 }}</ref>  However analyses that exclude trials of short duration (i.e. < 2 years) have demonstrated a survival benefit and are generally considered more clinically relevant.<ref>{{cite journal | vauthors = Shi J, Wu C, Lin Y, Chen YX, Zhu L, Xie WF | title = Long-term effects of mid-dose ursodeoxycholic acid in primary biliary cirrhosis: a meta-analysis of randomized controlled trials | journal = The American Journal of Gastroenterology | volume = 101 | issue = 7 | pages = 1529–1538 | date = July 2006 | pmid = 16863557 | doi = 10.1111/j.1572-0241.2006.00634.x | s2cid = 32076958 }}</ref> A Cochrane systematic review in 2012 found no significant benefit in reducing mortality, the rate of liver transplantation, [[pruritus]] or fatigue.<ref>{{cite journal | vauthors = Rudic JS, Poropat G, Krstic MN, Bjelakovic G, Gluud C | title = Ursodeoxycholic acid for primary biliary cirrhosis | journal = The Cochrane Database of Systematic Reviews | volume = 12 | issue = 12 | pages = CD000551 | date = December 2012 | pmid = 23235576 | pmc = 7045744 | doi = 10.1002/14651858.CD000551.pub3 }}</ref> Ursodiol and [[obeticholic acid]] are FDA-approved for the treatment of primary biliary cholangitis.<ref>{{cite journal | vauthors = Bowlus CL, Kenney JT, Rice G, Navarro R | title = Primary Biliary Cholangitis: Medical and Specialty Pharmacy Management Update | journal = Journal of Managed Care & Specialty Pharmacy | volume = 22 | issue = 10-a-s Suppl | pages = S3–S15 | date = October 2016 | pmid = 27700211 | doi = 10.18553/jmcp.2016.22.10-a-s.s3 | pmc = 10408407 | doi-access = free }}</ref>

===Primary sclerosing cholangitis===
UDCA use is associated with improved serum liver tests that do not always correlate with improved liver disease status.<ref>{{cite journal | vauthors = Poropat G, Giljaca V, Stimac D, Gluud C | title = Bile acids for primary sclerosing cholangitis | journal = The Cochrane Database of Systematic Reviews | volume = 2011 | issue = 1 | pages = CD003626 | date = January 2011 | pmid = 21249655 | pmc = 7163275 | doi = 10.1002/14651858.CD003626.pub2 }}</ref> WHO Drug Information advises against its use in primary sclerosing cholangitis in unapproved doses beyond 13–15&nbsp;mg/kg/day.<ref>{{cite journal | journal = WHO Drug Information | volume = 26 | issue = 1 | date = 2012 | title = Ursodeoxycholic acid: serious hepatic events | url =https://www.who.int/medicines/publications/druginformation/issues/26-1.pdf }}</ref>

UDCA in a dose of 28–30&nbsp;mg/kg/day increases risk of death and need for liver transplant by 2.3-fold among those with primary sclerosing cholangitis, despite decrease in liver enzymes.<ref>{{cite journal | vauthors = Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, Harnois D, Jorgensen R, Petz J, Keach J, Mooney J, Sargeant C, Braaten J, Bernard T, King D, Miceli E, Schmoll J, Hoskin T, Thapa P, Enders F | title = High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis | journal = Hepatology | volume = 50 | issue = 3 | pages = 808–814 | date = September 2009 | pmid = 19585548 | pmc = 2758780 | doi = 10.1002/hep.23082 }}</ref>

===Intrahepatic cholestasis of pregnancy===
UDCA has been used for [[intrahepatic cholestasis of pregnancy]]. UDCA lessens itching in the mother and may reduce the number of preterm births. Effects on fetal distress and other adverse outcomes are unlikely to be great.<ref>{{cite journal | vauthors = Walker KF, Chappell LC, Hague WM, Middleton P, Thornton JG | title = Pharmacological interventions for treating intrahepatic cholestasis of pregnancy | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 7 | pages = CD000493 | date = July 2020 | pmid = 32716060 | pmc = 7389072 | doi = 10.1002/14651858.CD000493.pub3 }}</ref><ref>{{cite journal | vauthors = Chappell LC, Bell JL, Smith A, Linsell L, Juszczak E, Dixon PH, Chambers J, Hunter R, Dorling J, Williamson C, Thornton JG | title = Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial | journal = Lancet | volume = 394 | issue = 10201 | pages = 849–860 | date = September 2019 | pmid = 31378395 | pmc = 6739598 | doi = 10.1016/S0140-6736(19)31270-X }}</ref>

===Cholestasis===
UDCA use is not licensed in children, as its safety and effectiveness have not been established. Evidence is accumulating that ursodeoxycholic acid is ineffective, unsafe and its use is associated with significant risk of morbidity and mortality in neonatal hepatitis and neonatal cholestasis.<ref>{{cite journal | vauthors = Kotb MA | title = Review of historical cohort: ursodeoxycholic acid in extrahepatic biliary atresia | journal = Journal of Pediatric Surgery | volume = 43 | issue = 7 | pages = 1321–1327 | date = July 2008 | pmid = 18639689 | doi = 10.1016/j.jpedsurg.2007.11.043 }}</ref><ref>{{cite book |author=Paediatric Formulary Committee |title=British National Formulary for Children 2008 |publisher=Pharmaceutical Press |location=London |year=2008 |page=91 |isbn=978-0-85369-780-0}}</ref><ref>{{cite web | title = Urso package insert. | location = Birmingham, AL | publisher = Axcan Pharma U.S. | date = January 2000 | url = http://www.axcan.com/pdf/urso_patient_brochure.pdf | access-date = 25 April 2009 | archive-date = 17 October 2006 | archive-url = https://web.archive.org/web/20061017072157/http://www.axcan.com/pdf/urso_patient_brochure.pdf | url-status = dead }}</ref><ref>{{cite journal | vauthors = Kotb MA, Mosallam D, Basanti CW, El Sorogy ST, Badr AM, Abd El Baky HE, Draz IH | title = Ursodeoxycholic acid use is associated with significant risk of morbidity and mortality in infants with cholestasis: A strobe compliant study | journal = Medicine | volume = 99 | issue = 7 | pages = e18730 | date = February 2020 | pmid = 32049781 | pmc = 7035015 | doi = 10.1097/MD.0000000000018730 }}</ref>

===Other conditions===
UDCA has been suggested to be an adequate treatment of bile reflux [[gastritis]].<ref name=newprb>{{cite journal | vauthors = McCabe ME, Dilly CK | title = New Causes for the Old Problem of Bile Reflux Gastritis | journal = Clinical Gastroenterology and Hepatology | volume = 16 | issue = 9 | pages = 1389–1392 | date = September 2018 | pmid = 29505908 | doi = 10.1016/j.cgh.2018.02.034 | hdl-access = free | s2cid = 3748071 | hdl = 1805/15771 }}</ref>

Ursodeoxycholic acid has been used to treat [[cystic fibrosis]]; however, a 2021 study aimed at evaluating whether the incidence of severe liver disease differed between CF centers routinely prescribing or not prescribing UDCA found no reduction in portal hypertension.<ref>{{cite journal | vauthors = Colombo C, Alicandro G, Oliver M, Lewindon PJ, Ramm GA, Ooi CY, Alghisi F, Kashirskaya N, Kondratyeva E, Corti F, Padoan R, Asherova I, Evans H, de Monestrol I, Strandvik B, Lindblad A | title = Ursodeoxycholic acid and liver disease associated with cystic fibrosis: A multicenter cohort study | journal = Journal of Cystic Fibrosis | volume = 21 | issue = 2 | pages = 220–226 | date = March 2022 | pmid = 33814323 | doi = 10.1016/j.jcf.2021.03.014 }}</ref>

UDCA has been in effective in [[non-alcoholic fatty liver disease]], in liver bile duct-paucity syndromes. It has been used as adjunct therapy in conditions with biliary tract obstruction such as [[biliary atresia]]; however liver transplant is often still required as definitive treatment for atresia. It is not effective in liver allograft rejection, and in [[graft-versus-host disease]] involving the liver.{{medical citation needed|date=October 2023}}

==Adverse effects==
Diarrhea was the most frequent adverse event seen in trial of UDCA in gallstone dissolution, occurring in 2 to 9%, which is less frequent than with [[chenodeoxycholic acid]] therapy. Bacterial conversion of UDCA to chenodeoxycholic acid may be the mechanism for this side effect. Right upper quadrant abdominal pain and exacerbation of pruritus was occasionally reported in trials in patients with PBC.<ref name="pmid14616161">{{cite journal | vauthors = Hempfling W, Dilger K, Beuers U | title = Systematic review: ursodeoxycholic acid--adverse effects and drug interactions | journal = Alimentary Pharmacology & Therapeutics | volume = 18 | issue = 10 | pages = 963–972 | date = November 2003 | pmid = 14616161 | doi = 10.1046/j.1365-2036.2003.01792.x | s2cid = 25738560 | doi-access = free }}</ref>  Additional symptoms may include bloating, weight gain, and occasionally, thinning of hair.<ref name=Lleo>{{cite journal | vauthors = Lleo A, Wang GQ, Gershwin ME, Hirschfield GM | title = Primary biliary cholangitis | journal = Lancet | volume = 396 | issue = 10266 | pages = 1915–1926 | date = December 2020 | pmid = 33308474 | doi = 10.1016/S0140-6736(20)31607-X | s2cid = 228086916 }}</ref>

==Mechanisms of action==

===Choleretic 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 [[digestion|digest]] [[fat]]s. Ursodeoxycholic acid helps regulate [[cholesterol]] by reducing the rate at which the [[intestine]] absorbs cholesterol molecules while breaking up [[micelle]]s containing cholesterol. The drug reduces cholesterol absorption and is used to dissolve (cholesterol) [[gallstone]]s in [[patient]]s who want an alternative to [[surgery]].<ref>{{cite journal | vauthors = Tint GS, Salen G, Shefer S | title = Effect of ursodeoxycholic acid and chenodeoxycholic acid on cholesterol and bile acid metabolism | journal = Gastroenterology | volume = 91 | issue = 4 | pages = 1007–1018 | date = October 1986 | pmid = 3527851 | doi = 10.1016/0016-5085(86)90708-0 | doi-access = free }}</ref> There are multiple mechanisms involved in cholestatic liver diseases.<ref name="PMID12198643">{{cite journal | vauthors = Paumgartner G, Beuers U | title = Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited | journal = Hepatology | volume = 36 | issue = 3 | pages = 525–531 | date = September 2002 | pmid = 12198643 | doi = 10.1053/jhep.2002.36088 | s2cid = 28282761 | doi-access = free }}</ref>

===Immunomodulating effects===
Ursodeoxycholic acid has also been shown experimentally to suppress [[immune system|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.<ref>{{cite web | work = Material Safety Data Sheet (MSDS) | title = Ursodiol | url = https://fscimage.fishersci.com/msds/70916.htm | publisher = Fisher Scientific }}</ref>

===Anti-inflammatory effects===
Ursodeoxycholic acid has been shown to exert anti-inflammatory and protective effects in human epithelial cells of the [[gastrointestinal tract]]. It has been linked to regulation of immunoregulatory responses by regulation of [[cytokine]]s,<ref>{{cite journal | vauthors = Ward JB, Lajczak NK, Kelly OB, O'Dwyer AM, Giddam AK, Ní Gabhann J, Franco P, Tambuwala MM, Jefferies CA, Keely S, Roda A, Keely SJ | title = Ursodeoxycholic acid and lithocholic acid exert anti-inflammatory actions in the colon | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 312 | issue = 6 | pages = G550–G558 | date = June 2017 | pmid = 28360029 | doi = 10.1152/ajpgi.00256.2016 | doi-access = free }}</ref> antimicrobial peptides [[defensin]]s,<ref>{{cite journal | vauthors = Lajczak NK, Saint-Criq V, O'Dwyer AM, Perino A, Adorini L, Schoonjans K, Keely SJ | title = Bile acids deoxycholic acid and ursodeoxycholic acid differentially regulate human β-defensin-1 and -2 secretion by colonic epithelial cells | journal = FASEB Journal | volume = 31 | issue = 9 | pages = 3848–3857 | date = September 2017 | pmid = 28487283 | doi = 10.1096/fj.201601365R | s2cid = 46877147 | doi-access =  free}}</ref> and take an active part in increased restitution of wound in the colon.<ref>{{cite journal | vauthors = Mroz MS, Lajczak NK, Goggins BJ, Keely S, Keely SJ | title = The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 314 | issue = 3 | pages = G378–G387 | date = March 2018 | pmid = 29351391 | doi = 10.1152/ajpgi.00435.2016 | s2cid = 3767047 }}</ref> Moreover, UDCA's effects has been shown to have exert actions outside the epithelial cells.<ref>{{cite journal | vauthors = O'Dwyer AM, Lajczak NK, Keyes JA, Ward JB, Greene CM, Keely SJ | title = Ursodeoxycholic acid inhibits TNFα-induced IL-8 release from monocytes | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 311 | issue = 2 | pages = G334–G341 | date = August 2016 | pmid = 27340129 | doi = 10.1152/ajpgi.00406.2015 | doi-access = free }}</ref>

While some bile acids are known to be colon tumor promoters (''e.g.'' [[deoxycholic acid]]),.<ref>Fogelson KA, Dorrestein PC, Zarrinpar A, Knight R (June 2023). "The gut microbial bile acid modulation and its relevance to digestive health and diseases". Gastroenterology. 164 (7): 1069–1085. doi:10.1053/j.gastro.2023.02.022. PMC 10205675. PMID 36841488.
</ref><ref>Bernstein H, Bernstein C (January 2023). "Bile acids as carcinogens in the colon and at other sites in the gastrointestinal system". Experimental Biology and Medicine (Maywood). 248 (1): 79–89. doi:10.1177/15353702221131858. PMC 9989147. PMID 36408538.</ref><ref>Yang S, Wang Y, Sheng L, Cui W, Ma C (January 2025). "The effect of fecal bile acids on the incidence and risk-stratification of colorectal cancer: an updated systematic review and meta-analysis". Scientific Reports. 15 (1): 740. Bibcode:2025NatSR..15..740Y. doi:10.1038/s41598-024-84801-6. PMC 11698987. PMID 39753873</ref> others such as ursodeoxycholic acid are thought to be [[Chemoprophylaxis|chemopreventive]], perhaps by inducing cellular differentiation and/or cellular senescence in colon epithelial cells.<ref>{{cite journal | vauthors = Akare S, Jean-Louis S, Chen W, Wood DJ, Powell AA, Martinez JD | title = Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence | journal = International Journal of Cancer | volume = 119 | issue = 12 | pages = 2958–2969 | date = December 2006 | pmid = 17019713 | doi = 10.1002/ijc.22231 | s2cid = 21187798 | doi-access =  }}</ref><ref>Kühn T, Stepien M, López-Nogueroles M, Damms-Machado A, Sookthai D, Johnson T, Roca M, Hüsing A, Maldonado SG, Cross AJ, Murphy N, Freisling H, Rinaldi S, Scalbert A, Fedirko V, Severi G, Boutron-Ruault MC, Mancini FR, Sowah SA, Boeing H, Jakszyn P, Sánchez MJ, Merino S, Colorado-Yohar S, Barricarte A, Khaw KT, Schmidt JA, Perez-Cornago A, Trichopoulou A, Karakatsani A, Thriskos P, Palli D, Agnoli C, Tumino R, Sacerdote C, Panico S, Bueno-de-Mesquita B, van Gils CH, Heath AK, Gunter MJ, Riboli E, Lahoz A, Jenab M, Kaaks R. Prediagnostic Plasma Bile Acid Levels and Colon Cancer Risk: A Prospective Study. J Natl Cancer Inst. 2020 May 1;112(5):516-524. doi: 10.1093/jnci/djz166. Erratum in: J Natl Cancer Inst. 2020 Oct 1;112(10):1077. doi: 10.1093/jnci/djaa094. PMID 31435679; PMCID: PMC7225675.</ref><ref>Alberts DS, Martínez ME, Hess LM, Einspahr JG, Green SB, Bhattacharyya AK, Guillen J, Krutzsch M, Batta AK, Salen G, Fales L, Koonce K, Parish D, Clouser M, Roe D, Lance P; Phoenix and Tucson Gastroenterologist Networks. Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. J Natl Cancer Inst. 2005 Jun 1;97(11):846-53. doi: 10.1093/jnci/dji144. PMID 15928305.</ref>

== Chemistry ==
Ursodeoxycholic acid is an [[epimer]] of [[chenodeoxycholic acid]], which has similar choleretic effects and a wider species distribution. However, CDCA is not as well-tolerated in humans and it does not show immunomodulating or chemoprotective effects. Both are 7-hydroxyl derivatives of deoxycholic acid, but UDCA has the group in the beta instead of the alpha orientation.<ref name="Feng"/>

=== Biosynthesis ===
Among mammals, only bears ([[Ursidae]]; excluding [[giant panda]]s) produce UDCA at useful amounts<ref name="Feng"/> (&gt;30%). It is produced in the bear liver, but the pathway remains unknown.<ref name="pmid8263415" />

Other vertebrates produce UDCA in much smaller amounts by gut bacteria. CDCA is oxidized into 7-oxo-CDCA then reduced into UDCA.<ref>{{cite journal | vauthors = Devlin AS, Fischbach MA | title = A biosynthetic pathway for a prominent class of microbiota-derived bile acids | journal = Nature Chemical Biology | volume = 11 | issue = 9 | pages = 685–690 | date = September 2015 | pmid = 26192599 | pmc = 4543561 | doi = 10.1038/nchembio.1864 }}</ref>

=== Industrial production ===
UDCA is most commonly produced from [[cholic acid]] (CA) derived from bovine bile, a by-product of the beef industry. The current yield of this [[semisynthesis]] is about 30%.<ref>{{cite journal | vauthors = Tonin F, Arends IW | title = Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review | journal = Beilstein Journal of Organic Chemistry | volume = 14 | pages = 470–483 | date = 2018 | pmid = 29520309 | pmc = 5827811 | doi = 10.3762/bjoc.14.33 | doi-access = free }}</ref>

== Society and culture ==

===Names===
The term is from the Latin noun ''[[wikt:ursus|ursus]]'' meaning bear, as [[bear bile]] contains the substance.<ref>{{cite web | url = https://pubchem.ncbi.nlm.nih.gov/compound/Ursodiol | title = Ursodiol | work = PubChem | publisher = U.S. National Library of Medicine }}</ref>

Ursodeoxycholic acid can be chemically synthesized and is marketed under multiple trade names, including Ursetor, Udikast, Actibile, Actigall,<ref name="Actigall FDA label"/> Biliver, Deursil, Egyurso, Heptiza 300/150, Stener, Udcasid, Udiliv, Udinorm, Udoxyl, Urso, Urso Forte, Ursocol, Ursoliv, Ursofalk,<ref>{{cite web | url = https://prehledy.sukl.cz/prehled_leciv.html#/detail-reg/0148926 | title = Ursofalk | work = Registered LP name | publisher = State Institute for Drug Control | location = Prague, Czech Republic|language=cs}}</ref> Ursosan, Ursoserinox, Udimarin, and Ursonova.{{citation needed|date=February 2020}}

=== History ===
Bear bile, a natural source of UDCA, is used in [[traditional Chinese medicine]] since the seventh century. Japanese scientists successfully synthesized UDCA chemically in 1955.<ref name="Feng">{{cite journal | vauthors = Feng Y, Siu K, Wang N, Ng KM, Tsao SW, Nagamatsu T, Tong Y | title = Bear bile: dilemma of traditional medicinal use and animal protection | journal = Journal of Ethnobiology and Ethnomedicine | volume = 5 | issue = 1 | pages = 2 | date = January 2009 | pmid = 19138420 | pmc = 2630947 | doi = 10.1186/1746-4269-5-2 | doi-access = free }}</ref> The earliest reference to UDCA in [[PubMed]] dates to 1957 under an alternative spelling "ursodesoxycholic acid", in a small-scale clinical trial.<ref>{{cite journal | vauthors = Arakawa T, Kagaya A, Inaba Y | title = Ursodesoxycholic acid as in accelerator for riboflavin phosphorylation in children with nutritional dystrophy | journal = The Journal of Vitaminology | volume = 3 | issue = 3 | pages = 165–167 | date = September 1957 | pmid = 13476545 | doi = 10.5925/jnsv1954.3.165 | doi-access = free }}</ref>

Ursodeoxycholic acid (application filed by [[Allergan]]) was approved for use in the United States in December 1987,<ref>{{cite web | title=Actigall: FDA-Approved Drugs | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019594 | archive-url=https://web.archive.org/web/20170125191420/http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=019594 | url-status=dead | archive-date=25 January 2017 | access-date=29 April 2020}}</ref> and was designated an [[orphan drug]].<ref>{{cite web | title=Actigall Orphan Drug Designation and Approval | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=55390 | archive-url=https://web.archive.org/web/20200809000039/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=55390 | url-status=dead | archive-date=9 August 2020 | access-date=29 April 2020}}</ref>

== References ==
{{Reflist}}

{{Bile and liver therapy}}
{{Portal bar | Medicine}}
{{Authority control}}

{{DEFAULTSORT:Ursodeoxycholic Acid}}
[[Category:Drugs developed by AbbVie]]
[[Category:Bile acids]]
[[Category:Cholanes]]
[[Category:Drugs acting on the gastrointestinal system and metabolism]]
[[Category:Orphan drugs]]