U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C24H40O4
Molecular Weight 392.5729
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of URSODIOL

SMILES

C[C@]([H])(CCC(=O)O)[C@@]1([H])CC[C@@]2([H])[C@@]3([H])[C@]([H])(CC[C@]12C)[C@@]4(C)CC[C@]([H])(C[C@@]4([H])C[C@]3([H])O)O

InChI

InChIKey=RUDATBOHQWOJDD-UZVSRGJWSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: description was created based on several sources, including: http://www.drugbank.ca/drugs/DB01586

Ursodiol tablets, USP are bile acids indicated for the treatment of patients with primary biliary cirrhosis. Ursodiol (Ursodeoxycholic acid), a naturally occurring hydrophilic bile acid, derived from cholesterol, is present as a minor fraction of the total human bile acid pool. Ursodeoxycholic 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. In addition to the replacement and displacement of toxic bile acids, other mechanisms of action include cytoprotection of the injured bile duct epithelial cells (cholangiocytes) against toxic effects of bile acids, inhibition of apotosis of hepatocytes, immunomodulatory effects, and stimulation of bile secretion by hepatocytes and cholangiocytes. Neither 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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Chenodiol

Approved Use

Chenodiol is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. The likelihood of successful dissolution is far greater if the stones are floatable or small. For patients with nonfloatable stones, dissolution is less likely and added weight should be given to the risk that more emergent surgery might result form a delay due to unsuccessful treatment.

Launch Date

4.28198396E11
Primary
URSODIOL

Approved Use

Ursodiol

Launch Date

6.1655037E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.2 μM
15 mg/kg bw 1 times / day multiple, oral
dose: 15 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
URSODIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
49.8 μM × h
15 mg/kg bw 1 times / day multiple, oral
dose: 15 mg/kg bw
route of administration: Oral
experiment type: MULTIPLE
co-administered:
URSODIOL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
50 mg/kg 3 times / day multiple, oral (total daily dose)
Highest studied dose
Dose: 50 mg/kg, 3 times / day
Route: oral
Route: multiple
Dose: 50 mg/kg, 3 times / day
Sources: Page: p.18
unhealthy, 37-65
n = 7
Health Status: unhealthy
Condition: Amyotrophic lateral sclerosis
Age Group: 37-65
Sex: M+F
Population Size: 7
Sources: Page: p.18
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 60
Health Status: unhealthy
Condition: Primary biliary cirrhosis
Population Size: 60
Sources: Page: p.4
Disc. AE: Nausea...
AEs leading to
discontinuation/dose reduction:
Nausea (1.7%)
Sources: Page: p.4
AEs

AEs

AESignificanceDosePopulation
Nausea 1.7%
Disc. AE
500 mg 2 times / day multiple, oral
Recommended
Dose: 500 mg, 2 times / day
Route: oral
Route: multiple
Dose: 500 mg, 2 times / day
Sources: Page: p.4
unhealthy
n = 60
Health Status: unhealthy
Condition: Primary biliary cirrhosis
Population Size: 60
Sources: Page: p.4
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [Inhibition 20 uM]
yes
no (co-administration study)
Comment: UDCA did not lead to detectable changes in midazolam pharmacokinetics
yes
weak (co-administration study)
Comment: UDCA modestly decreased digoxin disposition without
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Effects of clofibrate in primary biliary cirrhosis hypercholesterolemia and gallstones.
1975 Oct
Ursodeoxycholic acid treatment in children with Byler disease.
1999 Dec
Optimum dose of ursodeoxycholic acid in primary biliary cirrhosis.
1999 Oct
Genotoxic polycyclic aromatic hydrocarbon ortho-quinones generated by aldo-keto reductases induce CYP1A1 via nuclear translocation of the aryl hydrocarbon receptor.
2000 Feb 15
Ursodeoxycholic acid (UDCA) for the treatment of amoxycillin-clavulanate potassium (Augmentin)-induced intra-hepatic cholestasis: report of two cases.
2000 Mar
Differential modulation of cellular death and survival pathways by conjugated bile acids.
2001
[Experience in treatment of chronic toxic hepatitis by ursodeoxicholic acid].
2001
Primary biliary cirrhosis: from induction to destruction.
2001 Apr
Lichenoid eruptions due to ursodeoxycholic acid administration.
2001 Aug
Ursodiol prevents UC-associated CRC.
2001 Aug
The negative effects of bile acids and tumor necrosis factor-alpha on the transcription of cholesterol 7alpha-hydroxylase gene (CYP7A1) converge to hepatic nuclear factor-4: a novel mechanism of feedback regulation of bile acid synthesis mediated by nuclear receptors.
2001 Aug 17
Effect of bile acids on formation of azoxymethane-induced aberrant crypt foci in colostomized F344 rat colon.
2001 Aug 28
Anti-inflammatory effects of 5-aminosalicylic acid conjugates with chenodeoxycholic acid and ursodeoxycholic acid on carrageenan-induced colitis in guinea-pigs.
2001 Dec
Inducible microsomal prostaglandin E synthase is overexpressed in colorectal adenomas and cancer.
2001 Dec
Colonic luminal contents induce cyclooxygenase 2 transcription in human colon carcinoma cells.
2001 Feb
Novel bile acid derivatives induce apoptosis via a p53-independent pathway in human breast carcinoma cells.
2001 Feb 10
Determination of bile acids in biological fluids by liquid chromatography-electrospray tandem mass spectrometry.
2001 Jan
Ursodeoxycholic acid alone or with chenodeoxycholic acid for dissolution of cholesterol gallstones: a randomized multicentre trial. The British-Italian Gallstone Study group.
2001 Jan
Magnetic resonance imaging and spectroscopic changes in brains of patients with cerebrotendinous xanthomatosis.
2001 Jan
Use of ursodeoxycholic acid in liver diseases.
2001 Jan
[Ursodeoxycholic acid and prevention of tacrine-induced hepatotoxicity: a pilot study].
2001 Jan-Feb
Cerebrotendinous xanthomatosis presenting as "chologenic diarrhoea".
2001 Jul
Ursodeoxycholic acid 'mechanisms of action and clinical use in hepatobiliary disorders'.
2001 Jul
Fetal bile acid metabolism: analysis of urinary 3beta-monohydroxy-delta(5) bile acid in preterm infants.
2001 Jul
Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon.
2001 Jun
Expression of sterol 12alpha-hydroxylase alters bile acid pool composition in primary rat hepatocytes and in vivo.
2001 Jun
Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis.
2001 Jun
Deoxycholic acid suppresses p53 by stimulating proteasome-mediated p53 protein degradation.
2001 Jun
Low in vivo toxicity of a novel cisplatin-ursodeoxycholic derivative (Bamet-UD2) with enhanced cytostatic activity versus liver tumors.
2001 Jun
[Other antihyperlipidemic drugs with novel mechanism].
2001 Mar
Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration.
2001 Mar
Enhancement of endothelial nitric oxide production by chenodeoxycholic acids in patients with hepatobiliary diseases.
2001 May
Effects of treatment with deoxycholic acid and chenodeoxycholic acid on the hepatic synthesis of cholesterol and bile acids in healthy subjects.
2001 May
Autoimmune liver disease. Current standards, future directions.
2001 May
Isoursodeoxycholic acid: metabolism and therapeutic effects in primary biliary cirrhosis.
2001 May
Differences in the efficacy of ursodeoxycholic acid and bile acid metabolism between viral liver diseases and primary biliary cirrhosis.
2001 May
MDR3 gene defect in adults with symptomatic intrahepatic and gallbladder cholesterol cholelithiasis.
2001 May
Cerebrotendinous xanthomatosis.
2001 Nov 13
Predominance of human versus rat phenotype in the metabolic pathways for bile acid synthesis by hybrid WIF-B9 cells.
2001 Nov 30
Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression.
2001 Nov 9
External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice.
2001 Sep
Ursodeoxycholic acid and in vitro vasoactivity of hydrophobic bile acids.
2001 Sep
Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind, placebo-controlled trial on symptomatic patients.
2001 Sep
[Cerebrotendinous xanthomatosis].
2001 Sep 1
Guest-responsive fluorescence variations of gamma-cyclodextrins labeled with hetero-functionalized pyrene and tosyl moieties.
2002 Feb
MALDI-TOF-MS analysis of droplets prepared in an electrodynamic balance: "wall-less" sample preparation.
2002 Feb 1
Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism.
2002 Feb 7
Induction of cyclooxygenase-2 by tumor promoters in transformed and cytochrome P450 2E1-expressing hepatocytes.
2002 Jan
Differences in the regulation of the classical and the alternative pathway for bile acid synthesis in human liver. No coordinate regulation of CYP7A1 and CYP27A1.
2002 Jul 26
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dose range for Chenodiol is 13 to 16 mg/kg/day in two divided doses, morning and night, starting with 250 mg b.i.d. the first two weeks and increasing by 250 mg/day each week thereafter until the recommended or maximum tolerated dose is reached. If diarrhea occurs during dosage buildup or later in treatment, it usually can be controlled by temporary dosage adjustment until symptoms abate, after which the previous dosage usually is tolerated. Dosage less than 10 mg/kg usually is ineffective and may be associated with increased risk of cholecystectomy, so is not recommended.
Route of Administration: Oral
Hepatocytes were treated with Chenodiol at 10, 30, and 100 uM for 48 h, and RNA was extracted for real-time PCR analysis. Chenodiol markedly suppressed CYP7A1, the rate-limiting enzyme of bile acid synthesis, but only moderately (35%) down-regulated CYP8B1 at a high concentration of 100uM. Chenodiol increased the two major target genes of the farnesoid X receptor (FXR), namely the small heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth factor 19 (FGF19) over 100-fold.
Name Type Language
URSODIOL
INCI   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF  
INCI   USAN  
Official Name English
URSODEOXYCHOLIC ACID [MART.]
Common Name English
URSODEOXYCHOLIC ACID [EP]
Common Name English
NSC-683769
Code English
URSODIOL [USP MONOGRAPH]
Common Name English
URSODIOL [MI]
Common Name English
3.ALPHA.,7.BETA.-DIHYDROXY-5B-CHOLAN-24-OIC ACID
Common Name English
URSODEOXYCHOLIC ACID [WHO-DD]
Common Name English
URSODIOL [USAN]
Common Name English
URSODIOL [INCI]
Common Name English
URSO
Brand Name English
URSODESOXYCHOLIC ACID
Common Name English
URSODIOL [ORANGE BOOK]
Common Name English
URSODEOXYCHOLIC ACID [EP MONOGRAPH]
Common Name English
ACTIGALL
Common Name English
UDCA
Common Name English
URSODIOL [VANDF]
Common Name English
URSONORM
Brand Name English
URSODEOXYCHOLIC ACID
EP   INN   MART.   WHO-DD  
INN  
Official Name English
URSODEOXYCHOLIC ACID [INN]
Common Name English
CHOLAN-24-OIC ACID, 3,7-DIHYDROXY-, (3.ALPHA.,5.BETA.,7.BETA.)-
Common Name English
URSODIOL [USP-RS]
Common Name English
URSODEOXYCHOLATE
Common Name English
Classification Tree Code System Code
NDF-RT N0000006801
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
FDA ORPHAN DRUG 242607
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
FDA ORPHAN DRUG 55390
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
LOINC 55159-8
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
FDA ORPHAN DRUG 191204
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
NDF-RT N0000175802
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
WHO-VATC QA05AA02
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
FDA ORPHAN DRUG 22187
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
EU-Orphan Drug EU/3/17/1878
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
FDA ORPHAN DRUG 636718
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
NCI_THESAURUS C2089
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
LIVERTOX 1011
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
WHO-ATC A05AA02
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
NCI_THESAURUS C29703
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
Code System Code Type Description
LACTMED
Ursodiol
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
PUBCHEM
31401
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
USP_CATALOG
1707806
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY USP-RS
ECHA (EC/EINECS)
204-879-3
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
ChEMBL
CHEMBL1551
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
EPA CompTox
128-13-2
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
EVMPD
SUB11389MIG
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
MESH
D014580
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
FDA UNII
724L30Y2QR
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
CAS
128-13-2
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
RXCUI
62427
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
ALTERNATIVE
MERCK INDEX
M11344
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY Merck Index
NCI_THESAURUS
C1818
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
DRUG BANK
DB01586
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
IUPHAR
7104
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
DRUG CENTRAL
2797
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
INN
4920
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
RXCUI
11065
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY
WIKIPEDIA
URSODIOL
Created by admin on Fri Jun 25 20:57:46 UTC 2021 , Edited by admin on Fri Jun 25 20:57:46 UTC 2021
PRIMARY