Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H32F2O5 |
Molecular Weight | 390.4619 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC(=O)[C@H](CCCCCCC(O)=O)[C@@]1([H])CC[C@@](O)(O2)C(F)(F)CCCC
InChI
InChIKey=WGFOBBZOWHGYQH-MXHNKVEKSA-N
InChI=1S/C20H32F2O5/c1-2-3-11-19(21,22)20(26)12-10-15-14(16(23)13-17(15)27-20)8-6-4-5-7-9-18(24)25/h14-15,17,26H,2-13H2,1H3,(H,24,25)/t14-,15-,17-,20-/m1/s1
Molecular Formula | C20H32F2O5 |
Molecular Weight | 390.4619 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 4 / 4 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.drugbank.ca/drugs/DB01046Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/021908Orig1s008.pdf
Sources: http://www.drugbank.ca/drugs/DB01046
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/021908Orig1s008.pdf
Lubiprostone is a medication used in the management of idiopathic chronic constipation. It is a bicyclic fatty acid (prostaglandin E1 derivative) which acts by specifically activating ClC-2 chloride channels on the apical aspect of gastrointestinal epithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM). Lubiprostone acts by specifically activating ClC-2 chloride channels, which is a normal constituent of the apical membrane of the human intestine, in a protein kinase A action independent fashion. Activation of ClC-2 chloride channels causes an efflux of chloride ions into the lumen, which in turn leads to an efflux of sodium ions through a paracellular pathway to maintain isoelectric neutrality. As a result, water follows sodium into the lumen in order to maintain isotonic equilibrium, thereby increasing intestinal fluid secretion. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby increasing the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. Activation of ClC-2 chloride channels may also stimulate the recovery of muscosal barrier function by restoring tight junction protein complexes in the intestine. Patch clamp cell studies in human cell lines have indicated that the majority of the beneficial biological activity of lubiprostone and its metabolites is observed only on the apical (luminal) portion of the gastrointestinal epithelium. Lubiprostone is marketed under the trade name Amitiza among others.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1628478 |
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Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Amitiza Approved UseAmitiza is a chloride channel activator indicated for:
• Treatment of chronic idiopathic constipation in adults
• Treatment of irritable bowel syndrome with constipation in women ≥ 18 years old Launch Date1.13857921E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
41.5 pg/mL |
24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered: |
15-HYDROXY LUBIPROSTONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
37.5 pg/mL |
24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered: |
15-HYDROXY LUBIPROSTONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
57.1 pg × h/mL |
24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered: |
15-HYDROXY LUBIPROSTONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
39.6 pg × h/mL |
24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered: |
15-HYDROXY LUBIPROSTONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1.15 h |
24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered: |
15-HYDROXY LUBIPROSTONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6% |
24 μg single, oral dose: 24 μg route of administration: Oral experiment type: SINGLE co-administered: |
15-HYDROXY LUBIPROSTONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
24 ug 2 times / day multiple, oral Recommended Dose: 24 ug, 2 times / day Route: oral Route: multiple Dose: 24 ug, 2 times / day Sources: Page: p.1, 4 |
unhealthy n = 1113 Health Status: unhealthy Condition: Chronic idiopathic constipation Population Size: 1113 Sources: Page: p.1, 4 |
Disc. AE: Nausea, Dyspnea... AEs leading to discontinuation/dose reduction: Nausea (9%) Sources: Page: p.1, 4Dyspnea (2%) |
144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Other AEs: Nausea, Diarrhea... Other AEs: Nausea (45%) Sources: Page: p.8Diarrhea (35%) Vomiting (27%) Dizziness (14%) Headache (12%) Abdominal pain (8%) Flash hot (8%) Retching (8%) Dyspnea (4%) Pallor (4%) Stomach discomfort (4%) Anorexia (2%) Asthenia (2%) Chest discomfort (2%) Dry mouth (2%) Hyperhidrosis (2%) Syncope (2%) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Dyspnea | 2% Disc. AE |
24 ug 2 times / day multiple, oral Recommended Dose: 24 ug, 2 times / day Route: oral Route: multiple Dose: 24 ug, 2 times / day Sources: Page: p.1, 4 |
unhealthy n = 1113 Health Status: unhealthy Condition: Chronic idiopathic constipation Population Size: 1113 Sources: Page: p.1, 4 |
Nausea | 9% Disc. AE |
24 ug 2 times / day multiple, oral Recommended Dose: 24 ug, 2 times / day Route: oral Route: multiple Dose: 24 ug, 2 times / day Sources: Page: p.1, 4 |
unhealthy n = 1113 Health Status: unhealthy Condition: Chronic idiopathic constipation Population Size: 1113 Sources: Page: p.1, 4 |
Headache | 12% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Dizziness | 14% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Anorexia | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Asthenia | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Chest discomfort | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Dry mouth | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Hyperhidrosis | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Syncope | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Vomiting | 27% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Diarrhea | 35% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Dyspnea | 4% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Pallor | 4% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Stomach discomfort | 4% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Nausea | 45% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Abdominal pain | 8% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Flash hot | 8% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Retching | 8% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: Page: p.8 |
healthy n = 51 Health Status: healthy Population Size: 51 Sources: Page: p.8 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021908s000_Amitiza_BIOPHARMR.pdf Page: 6, 14, 19 |
no |
PubMed
Title | Date | PubMed |
---|---|---|
SPI-0211 activates T84 cell chloride transport and recombinant human ClC-2 chloride currents. | 2004 Nov |
|
Lubiprostone: RU 0211, SPI 0211. | 2005 |
|
Gateways to clinical trials. | 2005 May |
|
Lubiprostone. | 2005 May |
|
Treating chronic constipation : How should we interpret the recommendations? | 2006 |
|
Lubiprostone: viewpoints. | 2006 |
|
Lubiprostone. | 2006 |
|
Defecation disorders: neuromuscular aspects and treatment. | 2006 Aug |
|
Lubiprostone: chloride channel activator for chronic constipation. | 2006 Dec |
|
Gateways to clinical trials. | 2006 Jan-Feb |
|
Current gut-directed therapies for irritable bowel syndrome. | 2006 Jul |
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Chronic constipation: let symptom type and severity direct treatment. | 2006 Jul |
|
Lubiprostone (amitiza) for chronic constipation. | 2006 Jun 5 |
|
Effect of a selective chloride channel activator, lubiprostone, on gastrointestinal transit, gastric sensory, and motor functions in healthy volunteers. | 2006 May |
|
New drugs: lubiprostone, ranolazine, and anidulafungin. | 2006 May-Jun |
|
Gateways to clinical trials. | 2006 Sep |
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Lubiprostone: a chloride channel activator. | 2007 Apr |
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Chloride transporting capability of Calu-3 epithelia following persistent knockdown of the cystic fibrosis transmembrane conductance regulator, CFTR. | 2007 Apr |
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Lubiprostone: a new drug for the treatment of chronic idiopathic constipation. | 2007 Fall |
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New drugs 07, part I. | 2007 Feb |
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Drug approvals. | 2007 Feb |
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Recovery of mucosal barrier function in ischemic porcine ileum and colon is stimulated by a novel agonist of the ClC-2 chloride channel, lubiprostone. | 2007 Feb |
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Activation of type-2 chloride channels: a novel therapeutic target for the treatment of chronic constipation. | 2007 Jan |
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Constipation in long-term care. | 2007 May |
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Managing the chronically constipated adult: emerging approaches to diagnosis and treatment. | 2007 Sep |
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Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation. | 2008 Apr |
|
A synthetic prostone activates apical chloride channels in A6 epithelial cells. | 2008 Aug |
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Lubiprostone for constipation and irritable bowel syndrome with constipation. | 2008 Dec |
|
Lubiprostone: easing the strain of constipation? | 2008 Jan |
|
Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation. | 2008 Jan |
|
Conquering IBS in women: the clinician's pursuit of optimum management strategies. | 2008 Jul |
|
Development of drugs for gastrointestinal motor disorders: translating science to clinical need. | 2008 Mar |
|
[Functional and motor gastrointestinal disorders]. | 2008 Oct |
|
Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine. | 2008 Oct 21 |
|
Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model. | 2008 Oct 3 |
|
Management of constipation in the elderly: emerging therapeutic strategies. | 2008 Sep 7 |
|
Treatment of dysautonomia associated with Parkinson's disease. | 2009 Dec |
|
Lubiprostone: chronic constipation and irritable bowel syndrome with constipation. | 2009 Jan |
|
To the editor. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. | 2009 Jun |
|
[New drugs for the treatment of constipation]. | 2010 Jul |
Sample Use Guides
Chronic idiopathic constipation
• 24 mcg taken twice daily orally with food and water
Irritable bowel syndrome with constipation
• 8 mcg taken twice daily orally with food and water
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19179625
Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evokes increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evokes increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM
Substance Class |
Chemical
Created
by
admin
on
Edited
Thu Jul 06 22:12:54 UTC 2023
by
admin
on
Thu Jul 06 22:12:54 UTC 2023
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Record UNII |
7662KG2R6K
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000175456
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WHO-VATC |
QA06AX03
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WHO-ATC |
A06AX03
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LIVERTOX |
NBK548000
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NCI_THESAURUS |
C78568
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NDF-RT |
N0000175573
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100000124449
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CHEMBL1201134
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157920
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M6919
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7662KG2R6K
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623033
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Lubiprostone
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4123
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DB01046
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C506401
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4242
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333963-40-9
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7662KG2R6K
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SUB32077
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DTXSID5048639
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NN-66
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C66040
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Lubiprostone
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136790-76-6
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EXCRETED UNCHANGED |
The radioactive dose was primarily excreted in urine via the kidneys (63% of the radiolabeled dose), while around 32% of the radiolabeled dose was excreted in feces.
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METABOLITE ACTIVE -> PARENT |
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IMPURITY -> PARENT |
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ACTIVE MOIETY |
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Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Tmax | PHARMACOKINETIC |
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