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Identification
NameUrsodeoxycholic acid
Accession NumberDB01586
Typesmall molecule
Groupsapproved, investigational
Description

Ursodeoxycholic acid is an epimer of chenodeoxycholic acid (DB06777). It is a mammalian bile acid found first in the bear and is apparently either a precursor or a product of chenodeoxycholate. Its administration changes the composition of bile and may dissolve gallstones. It is used as a cholagogue and choleretic. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
(3alpha,5beta,7beta)-3,7-dihydroxycholan-24-oic acidNot AvailableNot Available
(3α,5β,7β)-3,7-dihydroxycholan-24-oic acidNot AvailableNot Available
3alpha,7beta-Dihydroxy-5beta-cholan-24-oic acidNot AvailableNot Available
Acide ursodesoxycholiqueFrenchINN
Acido ursodeossicolicoItalianNot Available
Acido ursodeoxicolicoSpanishINN
Acidum ursodeoxycholicumLatinINN
ActigallNot AvailableNot Available
UDCANot AvailableNot Available
UrsodeoxycholateNot AvailableNot Available
Ursodeoxycholic acidNot AvailableNot Available
UrsodiolNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
ActigallNot Available
Cholit-ursanNot Available
DelursanNot Available
DestolitNot Available
DeursilNot Available
LitursolNot Available
SolutratNot Available
UrsacolNot Available
UrsoNot Available
Urso forteNot Available
UrsocholNot Available
UrsofalkNot Available
UrsolvanNot Available
Brand mixturesNot Available
Categories
CAS number128-13-2
WeightAverage: 392.572
Monoisotopic: 392.292659768
Chemical FormulaC24H40O4
InChI KeyRUDATBOHQWOJDD-UZVSRGJWSA-N
InChI
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
IUPAC Name
(4R)-4-[(1S,2S,5R,7S,9S,10R,11S,14R,15R)-5,9-dihydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-yl]pentanoic acid
SMILES
[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])CC[C@]12C)[C@H](C)CCC(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassBile Acids, Alcohols and Derivatives
Direct parentDihydroxy Bile Acids, Alcohols and Derivatives
Alternative parentsHydroxysteroids; Cyclohexanols; Cyclic Alcohols and Derivatives; Enolates; Polyamines; Carboxylic Acids
Substituents7-hydroxy-steroid; 3-hydroxy-steroid; cyclohexanol; cyclic alcohol; secondary alcohol; polyamine; enolate; carboxylic acid; carboxylic acid derivative; alcohol
Classification descriptionThis compound belongs to the dihydroxy bile acids, alcohols and derivatives. These are compounds containing or derived from a bile acid or alcohol, and which bears exactly two carboxylic acid groups.
Pharmacology
IndicationThe drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery.
PharmacodynamicsUrsodiol (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 gall bladder. When secreted into the colon, 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 gall stones non-surgically.
Mechanism of actionUrsodeoxycholic acid reduces elevated liver enzyme levels by facilitating bile flow through the liver and protecting liver cells. The main mechanism if anticholelithic. Although the exact process of ursodiol's anticholelithic action is not completely understood, it is thought that the drug is concentrated in bile and decreases biliary cholesterol by suppressing hepatic synthesis and secretion of cholesterol and by inhibiting its intestinal absorption. The reduced cholesterol saturation permits the gradual solubilization of cholesterol from gallstones, resulting in their eventual dissolution.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationOnly small quantities of ursodiol appear in the systemic circulation and very small amounts are excreted into urine. Eighty percent of lithocholic acid formed in the small bowel is excreted in the feces, but the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to relatively insoluble lithocholyl conjugates which are excreted into bile and lost in feces.
Half lifeNot Available
ClearanceNot Available
ToxicityNeither accidental nor intentional overdosing with ursodeoxycholic acid has been reported. Doses of ursodeoxycholic acid in the range of 16-20 mg/kg/day have been tolerated for 6-37 months without symptoms by 7 patients. The LD50 for ursodeoxycholic acid in rats is over 5000 mg/kg given over 7-10 days and over 7500 mg/kg for mice. The most likely manifestation of severe overdose with ursodeoxycholic acid would probably be diarrhea, which should be treated symptomatically.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9766
Blood Brain Barrier + 0.9288
Caco-2 permeable + 0.73
P-glycoprotein substrate Substrate 0.6648
P-glycoprotein inhibitor I Non-inhibitor 0.8737
P-glycoprotein inhibitor II Inhibitor 0.5368
Renal organic cation transporter Non-inhibitor 0.8537
CYP450 2C9 substrate Non-substrate 0.7818
CYP450 2D6 substrate Non-substrate 0.9115
CYP450 3A4 substrate Substrate 0.7407
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9456
CYP450 2D6 substrate Non-inhibitor 0.9781
CYP450 2C19 substrate Non-inhibitor 0.9707
CYP450 3A4 substrate Non-inhibitor 0.8405
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9563
Ames test Non AMES toxic 0.8794
Carcinogenicity Non-carcinogens 0.9329
Biodegradation Not ready biodegradable 0.992
Rat acute toxicity 2.5624 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9622
hERG inhibition (predictor II) Non-inhibitor 0.7246
Pharmacoeconomics
Manufacturers
  • Watson pharmaceuticals inc
  • Corepharma llc
  • Epic pharma llc
  • Lannett holdings inc
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa
  • Axcan pharma us inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Urso forte 500 mg tablet6.3USDtablet
Actigall 300 mg capsule5.52USDcapsule
Ursodiol 500 mg tablet4.75USDtablet
Urso 250 mg tablet4.41USDtablet
Urso 250 250 mg tablet3.55USDtablet
Urso Ds 500 mg Tablet2.69USDtablet
Ursodiol 250 mg tablet2.68USDtablet
Pms-Ursodiol C 500 mg Tablet1.75USDtablet
Urso 250 mg Tablet1.42USDtablet
Pms-Ursodiol C 250 mg Tablet0.92USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point203 °CPhysProp
water solubility20 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.00RODA,A ET AL. (1990)
Predicted Properties
PropertyValueSource
water solubility1.97e-02 g/lALOGPS
logP3.01ALOGPS
logP3.71ChemAxon
logS-4.3ALOGPS
pKa (strongest acidic)4.6ChemAxon
pKa (strongest basic)-0.54ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count4ChemAxon
hydrogen donor count3ChemAxon
polar surface area77.76ChemAxon
rotatable bond count4ChemAxon
refractivity109.27ChemAxon
polarizability46.33ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Antonio Bonaldi, Egidio Molinari, “Process for preparing high purity ursodeoxycholic acid.” U.S. Patent US4379093, issued July, 1980.

US4379093
General Reference
  1. Akare S, Jean-Louis S, Chen W, Wood DJ, Powell AA, Martinez JD: Ursodeoxycholic acid modulates histone acetylation and induces differentiation and senescence. Int J Cancer. 2006 Dec 15;119(12):2958-69. Pubmed
  2. Smith T, Befeler AS: High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Curr Gastroenterol Rep. 2007 Mar;9(1):54-9. Pubmed
  3. Jackson H, Solaymani-Dodaran M, Card TR, Aithal GP, Logan R, West J: Influence of ursodeoxycholic acid on the mortality and malignancy associated with primary biliary cirrhosis: A population-based cohort study. Hepatology. 2007 Aug 8;46(4):1131-1137. Pubmed
External Links
ResourceLink
KEGG DrugD00734
KEGG CompoundC07880
PubChem Compound31401
PubChem Substance46508795
ChemSpider29131
ChEBI9907
ChEMBLCHEMBL1551
Therapeutic Targets DatabaseDNC000420
PharmGKBPA451837
HETIU5
Drug Product Database2238984
WikipediaUrsodiol
ATC CodesA05AA02
AHFS Codes
  • 56:14.00
PDB Entries
FDA labelshow(233 KB)
MSDSshow(73.3 KB)
Interactions
Drug Interactions
Drug
CholestyramineThe resin decreases the effect of ursodiol
ClofibrateThe fibric acid derivative decreases the effect of ursodiol
ClomifeneEstrogens decreases the effect of ursodiol
ColesevelamBile Acid Sequestrants may decrease the serum concentration of Ursodiol. Consider administration of ursodiol 5 hours or more after bile acid sequestrants to minimize ursodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of ursodiol in patients receiving bile acid sequestrants.
ColestipolThe resin decreases the effect of ursodiol
Conjugated EstrogensEstrogens decreases the effect of ursodiol
CyclosporineUrsodiol increases the levels of cyclosporine
DiethylstilbestrolEstrogens decreases the effect of ursodiol
EstradiolEstrogens decreases the effect of ursodiol
Ethinyl EstradiolEstrogens decreases the effect of ursodiol
FenofibrateThe fibric acid derivative decreases the effect of ursodiol
GemfibrozilThe fibric acid derivative decreases the effect of ursodiol
Food InteractionsNot Available

Targets

1. Aldo-keto reductase family 1 member C2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inducer

Components

Name UniProt ID Details
Aldo-keto reductase family 1 member C2 P52895 Details

References:

  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Amaral JD, Sola S, Steer CJ, Rodrigues CM: Role of nuclear steroid receptors in apoptosis. Curr Med Chem. 2009;16(29):3886-902. Pubmed

Enzymes

1. Cytochrome P450 2E1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2E1 P05181 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Bile salt export pump

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Bile salt export pump O95342 Details

References:

  1. Schuetz EG, Strom S, Yasuda K, Lecureur V, Assem M, Brimer C, Lamba J, Kim RB, Ramachandran V, Komoroski BJ, Venkataramanan R, Cai H, Sinal CJ, Gonzalez FJ, Schuetz JD: Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. J Biol Chem. 2001 Oct 19;276(42):39411-8. Epub 2001 Aug 16. Pubmed
  2. Green RM, Hoda F, Ward KL: Molecular cloning and characterization of the murine bile salt export pump. Gene. 2000 Jan 4;241(1):117-23. Pubmed
  3. Mita S, Suzuki H, Akita H, Stieger B, Meier PJ, Hofmann AF, Sugiyama Y: Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G159-67. Epub 2004 Aug 5. Pubmed

2. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

References:

  1. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Pojer C, Zenz R, Lammert F, Stieger B, Meier PJ, Zatloukal K, Denk H, Trauner M: Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology. 2001 Jul;121(1):170-83. Pubmed
  2. Kullak-Ublick GA, Hagenbuch B, Stieger B, Schteingart CD, Hofmann AF, Wolkoff AW, Meier PJ: Molecular and functional characterization of an organic anion transporting polypeptide cloned from human liver. Gastroenterology. 1995 Oct;109(4):1274-82. Pubmed
  3. Kullak-Ublick GA, Hagenbuch B, Stieger B, Wolkoff AW, Meier PJ: Functional characterization of the basolateral rat liver organic anion transporting polypeptide. Hepatology. 1994 Aug;20(2):411-6. Pubmed
  4. Hata S, Wang P, Eftychiou N, Ananthanarayanan M, Batta A, Salen G, Pang KS, Wolkoff AW: Substrate specificities of rat oatp1 and ntcp: implications for hepatic organic anion uptake. Am J Physiol Gastrointest Liver Physiol. 2003 Nov;285(5):G829-39. Epub 2003 Jul 3. Pubmed

3. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM, Edwards PA: Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. J Biol Chem. 2002 Jan 25;277(4):2908-15. Epub 2001 Nov 12. Pubmed
  2. Fickert P, Zollner G, Fuchsbichler A, Stumptner C, Pojer C, Zenz R, Lammert F, Stieger B, Meier PJ, Zatloukal K, Denk H, Trauner M: Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. Gastroenterology. 2001 Jul;121(1):170-83. Pubmed

4. Multidrug resistance-associated protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance-associated protein 4 O15439 Details

References:

  1. Rius M, Nies AT, Hummel-Eisenbeiss J, Jedlitschky G, Keppler D: Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Hepatology. 2003 Aug;38(2):374-84. Pubmed

5. Ileal sodium/bile acid cotransporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Ileal sodium/bile acid cotransporter Q12908 Details

References:

  1. Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA: Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69. Pubmed
  2. Saeki T, Matoba K, Furukawa H, Kirifuji K, Kanamoto R, Iwami K: Characterization, cDNA cloning, and functional expression of mouse ileal sodium-dependent bile acid transporter. J Biochem. 1999 Apr;125(4):846-51. Pubmed
  3. Saeki T, Takahashi N, Kanamoto R, Iwami K: Characterization of cloned mouse Na+/taurocholate cotransporting polypeptide by transient expression in COS-7 cells. Biosci Biotechnol Biochem. 2002 May;66(5):1116-8. Pubmed

6. Sodium/bile acid cotransporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Sodium/bile acid cotransporter Q14973 Details

References:

  1. Boyer JL, Ng OC, Ananthanarayanan M, Hofmann AF, Schteingart CD, Hagenbuch B, Stieger B, Meier PJ: Expression and characterization of a functional rat liver Na+ bile acid cotransport system in COS-7 cells. Am J Physiol. 1994 Mar;266(3 Pt 1):G382-7. Pubmed
  2. Mita S, Suzuki H, Akita H, Stieger B, Meier PJ, Hofmann AF, Sugiyama Y: Vectorial transport of bile salts across MDCK cells expressing both rat Na+-taurocholate cotransporting polypeptide and rat bile salt export pump. Am J Physiol Gastrointest Liver Physiol. 2005 Jan;288(1):G159-67. Epub 2004 Aug 5. Pubmed

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Drug created on August 29, 2007 08:57 / Updated on January 11, 2014 20:13