Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C24H40O4.H2O4S |
| Molecular Weight | 490.65 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 10 / 10 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OS(O)(=O)=O.[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
InChI
InChIKey=NTHFOQKLSZUQTR-FUXQPCDDSA-N
InChI=1S/C24H40O4.H2O4S/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;1-5(2,3)4/h14-20,22,25-26H,4-13H2,1-3H3,(H,27,28);(H2,1,2,3,4)/t14-,15+,16-,17-,18+,19+,20+,22+,23+,24-;/m1./s1
DescriptionCurator's Comment: description was created based on several sources, including:
http://www.drugbank.ca/drugs/DB01586
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.
CNS Activity
Approval Year
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
15.2 μM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22414767 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
49.8 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22414767 |
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
| Dose | Population | Adverse 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
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical 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 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| [Ursodeoxycholic acid as the main treatment of hepatobiliary diseases in children and teenagers]. | 2001 |
|
| Suppression of renal disease and mortality in the female NZB x NZW F1 mouse model of systemic lupus erythematosus (SLE) by chenodeoxycholic acid. | 2001 |
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| Ursodeoxycholic acid for the treatment of intrahepatic cholestasis of pregnancy. | 2001 Apr |
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| Primary biliary cirrhosis: from induction to destruction. | 2001 Apr |
|
| Genetic disorders and molecular mechanisms in cholestatic liver disease--a clinical approach. | 2001 Apr |
|
| Drug-induced cholestasis. | 2001 Apr |
|
| Primary sclerosing cholangitis. | 2001 Apr |
|
| Prevention of colon cancer with ursodiol in ulcerative colitis. | 2001 Aug |
|
| Lichenoid eruptions due to ursodeoxycholic acid administration. | 2001 Aug |
|
| Ursodiol prevents UC-associated CRC. | 2001 Aug |
|
| Ursodeoxycholic acid causing exacerbation of dermatitis herpetiformis. | 2001 Aug |
|
| Jaundice in non-cirrhotic primary biliary cirrhosis: the premature ductopenic variant. | 2001 Aug |
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| Stimulation of ATP secretion in the liver by therapeutic bile acids. | 2001 Aug 15 |
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| Micronuclei induction, cell cycle delay and apoptosis as markers of cellular stress caused by ursodeoxycholic acid in human lymphocytes. | 2001 Aug 22 |
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| Effect of bile acids on formation of azoxymethane-induced aberrant crypt foci in colostomized F344 rat colon. | 2001 Aug 28 |
|
| Functional modulation of the glucocorticoid receptor and suppression of NF-kappaB-dependent transcription by ursodeoxycholic acid. | 2001 Dec 14 |
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| Treatment of primary biliary cirrhosis. | 2001 Jan-Dec |
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| Fetal bile acid metabolism: analysis of urinary 3beta-monohydroxy-delta(5) bile acid in preterm infants. | 2001 Jul |
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| Rapid progress of acute suppurative cholangitis to secondary sclerosing cholangitis sequentially followed-up by endoscopic retrograde cholangiography. | 2001 Jul |
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| A case of autoimmune hepatitis with a high titer of antimitochondrial antibody and normal gamma-globulinemia. | 2001 Jul |
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| Effects of ursodeoxycholic and cholic acid feeding on hepatocellular transporter expression in mouse liver. | 2001 Jul |
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| Prevention and treatment of veno-occlusive disease. | 2001 Jul-Aug |
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| Effect of bile acids on the proliferative activity and apoptosis of rat hepatocytes. | 2001 Jun |
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| Effect of ursodeoxycholate in University of Wisconsin solution on long term preservation of rat livers. | 2001 Jun |
|
| Ofloxacin and ursodeoxycholic acid versus ursodeoxycholic acid alone to prevent occlusion of biliary stents: a prospective, randomized trial. | 2001 Jun |
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| Effect of bezafibrate in primary biliary cirrhosis: a pilot study. | 2001 Jun |
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| Effect of bile salts on colonic mucus secretion in isolated vascularly perfused rat colon. | 2001 Jun |
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| Alterations in tight junctions differ between primary biliary cirrhosis and primary sclerosing cholangitis. | 2001 Jun |
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| Deoxycholic acid suppresses p53 by stimulating proteasome-mediated p53 protein degradation. | 2001 Jun |
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| Low in vivo toxicity of a novel cisplatin-ursodeoxycholic derivative (Bamet-UD2) with enhanced cytostatic activity versus liver tumors. | 2001 Jun |
|
| Bile acid hydrophobicity is correlated with induction of apoptosis and/or growth arrest in HCT116 cells. | 2001 Jun 1 |
|
| [3 beta-Hydroxysteroid-delta 5-oxidoreductase/isomerase deficiency]. | 2001 Mar |
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| [Effects of bile acid preparations on DNA biosynthesis, apoptosis, and necrosis in hepatocytes in vitro]. | 2001 Mar-Apr |
|
| Enhancement of endothelial nitric oxide production by chenodeoxycholic acids in patients with hepatobiliary diseases. | 2001 May |
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| Synthetic bile acid derivatives induce nonapoptotic death of human retinal pigment epithelial cells. | 2001 May |
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| Ursodeoxycholic acid for primary biliary cirrhosis: lesson for the future? | 2001 May |
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| Cytokine network in nonresponding chronic hepatitis C patients with genotype 1: role of triple therapy with interferon alpha, ribavirin, and ursodeoxycholate. | 2001 May |
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| Autoimmune liver disease. Current standards, future directions. | 2001 May |
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| High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis. | 2001 May |
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| Isoursodeoxycholic acid: metabolism and therapeutic effects in primary biliary cirrhosis. | 2001 May |
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| Differences in the efficacy of ursodeoxycholic acid and bile acid metabolism between viral liver diseases and primary biliary cirrhosis. | 2001 May |
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| A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis. | 2001 Oct |
|
| Antiepileptic drugs increase plasma levels of 4beta-hydroxycholesterol in humans: evidence for involvement of cytochrome p450 3A4. | 2001 Oct 19 |
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| Disrupted bile acid homeostasis reveals an unexpected interaction among nuclear hormone receptors, transporters, and cytochrome P450. | 2001 Oct 19 |
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| The natural history of primary biliary cirrhosis: of genes and cooperation. | 2001 Sep |
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| Apolipoprotein E polymorphism, a marker of disease severity in primary biliary cirrhosis? | 2001 Sep |
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| Ursodeoxycholic acid and in vitro vasoactivity of hydrophobic bile acids. | 2001 Sep |
|
| Geranylgeraniol, an intermediate product in mevalonate pathway, induces apoptotic cell death in human hepatoma cells: death receptor-independent activation of caspase-8 with down-regulation of Bcl-xL expression. | 2001 Sep |
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| Ten-year combination treatment with colchicine and ursodeoxycholic acid for primary biliary cirrhosis: a double-blind, placebo-controlled trial on symptomatic patients. | 2001 Sep |
|
| Biliary excretion of tauroursodeoxycholate-3-sulfate in the rat. | 2001 Sep |
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163203609
Created by
admin on Sat Dec 16 18:20:02 GMT 2023 , Edited by admin on Sat Dec 16 18:20:02 GMT 2023
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PRIMARY | |||
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84SS8Q4EEQ
Created by
admin on Sat Dec 16 18:20:02 GMT 2023 , Edited by admin on Sat Dec 16 18:20:02 GMT 2023
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130588-30-6
Created by
admin on Sat Dec 16 18:20:02 GMT 2023 , Edited by admin on Sat Dec 16 18:20:02 GMT 2023
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NON-SPECIFIC STOICHIOMETRY |
ACTIVE MOIETY
SUBSTANCE RECORD
