Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C20H32F2O5 |
Molecular Weight | 390.4627 |
Optical Activity | ( - ) |
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 | 390.4627 |
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 Date2006 |
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% |
LUBIPROSTONE plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
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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: |
unhealthy Health Status: unhealthy Sources: |
Disc. AE: Nausea, Dyspnea... AEs leading to discontinuation/dose reduction: Nausea (9%) Sources: Dyspnea (2%) |
144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Other AEs: Nausea, Diarrhea... Other AEs: Nausea (45%) Sources: Diarrhea (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: |
unhealthy Health Status: unhealthy Sources: |
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: |
unhealthy Health Status: unhealthy Sources: |
Headache | 12% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Dizziness | 14% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Anorexia | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Asthenia | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Chest discomfort | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Dry mouth | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Hyperhidrosis | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Syncope | 2% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Vomiting | 27% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Diarrhea | 35% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Dyspnea | 4% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Pallor | 4% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Stomach discomfort | 4% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Nausea | 45% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Abdominal pain | 8% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Flash hot | 8% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
Retching | 8% | 144 ug single, oral Studied dose Dose: 144 ug Route: oral Route: single Dose: 144 ug Sources: |
healthy Health Status: healthy Sources: |
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 |
|
Lubiprostone. | 2005 May |
|
Treating chronic constipation : How should we interpret the recommendations? | 2006 |
|
Lubiprostone. | 2006 |
|
Current gut-directed therapies for irritable bowel syndrome. | 2006 Jul |
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Gateways to clinical trials. | 2006 Sep |
|
Chloride transporting capability of Calu-3 epithelia following persistent knockdown of the cystic fibrosis transmembrane conductance regulator, CFTR. | 2007 Apr |
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Drug approvals. | 2007 Feb |
|
Review of the treatment options for chronic constipation. | 2007 May 2 |
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Lubiprostone: a novel treatment for chronic constipation. | 2008 |
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Lubiprostone for chronic idiopathic constipation and irritable bowel syndrome with constipation. | 2008 Aug |
|
A synthetic prostone activates apical chloride channels in A6 epithelial cells. | 2008 Aug |
|
Pharmacologic treatment of constipation: what is new? | 2008 Dec |
|
Opioid-induced bowel dysfunction. | 2008 Feb |
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Lubiprostone: easing the strain of constipation? | 2008 Jan |
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Pharmaceutical approval update. | 2008 Jun |
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Lubiprostone activates non-CFTR-dependent respiratory epithelial chloride secretion in cystic fibrosis mice. | 2008 Nov |
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Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model. | 2008 Oct 3 |
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Single-dose lubiprostone along with split-dose PEG solution without dietary restrictions for bowel cleansing prior to colonoscopy: a randomized, double-blind, placebo-controlled trial. | 2008 Sep |
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Management of constipation in the elderly: emerging therapeutic strategies. | 2008 Sep 7 |
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Constipation in the elderly: management strategies. | 2009 |
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Treatment of dysautonomia associated with Parkinson's disease. | 2009 Dec |
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The FDA and IBS drug development. | 2009 Dec |
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Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects. | 2009 Feb |
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Pathogenesis and management of irritable bowel syndrome. | 2009 Jan-Mar |
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A 73-year-old man with long-term immobility presenting with abdominal pain. | 2009 Jul 14 |
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To the editor. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. | 2009 Jun |
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Lubiprostone neither decreases gastric and small-bowel transit time nor improves visualization of small bowel for capsule endoscopy: a double-blind, placebo-controlled study. | 2009 Nov |
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Lubiprostone stimulates duodenal bicarbonate secretion in rats. | 2009 Oct |
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Management of irritable bowel syndrome. | 2009 Sep |
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Efficacy and safety of lubiprostone in patients with chronic constipation. | 2010 Apr |
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Update on the management of constipation in the elderly: new treatment options. | 2010 Aug 9 |
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Dynamic [Cl(-)](i) measurement with chloride sensing quantum dots nanosensor in epithelial cells. | 2010 Feb 5 |
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Review article: new receptor targets for medical therapy in irritable bowel syndrome. | 2010 Jan |
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Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia. | 2010 Jan 26 |
|
[New drugs for the treatment of constipation]. | 2010 Jul |
|
Lubiprostone reverses the inhibitory action of morphine on intestinal secretion in guinea pig and mouse. | 2010 Jul |
|
Emerging new therapeutic options for the management of opioid induced constipation. | 2010 Mar |
|
Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series. | 2010 Mar |
|
Enteric nervous system: sensory physiology, diarrhea and constipation. | 2010 Mar |
|
Emerging pharmacologic therapies for irritable bowel syndrome. | 2010 Oct |
|
Pharmacologic management of chronic constipation. | 2010 Sep |
|
Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype. | 2010 Sep 15 |
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
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on
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Wed Apr 02 08:21:40 GMT 2025
by
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on
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Record UNII |
7662KG2R6K
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Record Status |
FAILED
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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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CHEMBL1201134
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157920
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m6919
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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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333963-40-9
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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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BINDING
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TARGET -> ACTIVATOR |
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METABOLITE ACTIVE -> PARENT |
MAJOR
PLASMA
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METABOLITE -> 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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