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 |
||
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 |
|---|---|---|
| Emerging pharmacologic therapies for irritable bowel syndrome. | 2010-10 |
|
| Lubiprostone ameliorates the cystic fibrosis mouse intestinal phenotype. | 2010-09-15 |
|
| Pharmacologic management of chronic constipation. | 2010-09 |
|
| Update on the management of constipation in the elderly: new treatment options. | 2010-08-09 |
|
| [New drugs for the treatment of constipation]. | 2010-07 |
|
| Lubiprostone reverses the inhibitory action of morphine on intestinal secretion in guinea pig and mouse. | 2010-07 |
|
| Efficacy and safety of lubiprostone in patients with chronic constipation. | 2010-04 |
|
| Emerging new therapeutic options for the management of opioid induced constipation. | 2010-03 |
|
| Use of the chloride channel activator lubiprostone for constipation in adults with cystic fibrosis: a case series. | 2010-03 |
|
| Enteric nervous system: sensory physiology, diarrhea and constipation. | 2010-03 |
|
| Dynamic [Cl(-)](i) measurement with chloride sensing quantum dots nanosensor in epithelial cells. | 2010-02-05 |
|
| Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia. | 2010-01-26 |
|
| Review article: new receptor targets for medical therapy in irritable bowel syndrome. | 2010-01 |
|
| Treatment of dysautonomia associated with Parkinson's disease. | 2009-12 |
|
| The FDA and IBS drug development. | 2009-12 |
|
| Lubiprostone neither decreases gastric and small-bowel transit time nor improves visualization of small bowel for capsule endoscopy: a double-blind, placebo-controlled study. | 2009-11 |
|
| Lubiprostone stimulates duodenal bicarbonate secretion in rats. | 2009-10 |
|
| Management of irritable bowel syndrome. | 2009-09 |
|
| Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator. | 2009-09 |
|
| Pathogenesis and management of irritable bowel syndrome. | 2009-07-24 |
|
| A 73-year-old man with long-term immobility presenting with abdominal pain. | 2009-07-14 |
|
| Lubiprostone: in constipation-predominant irritable bowel syndrome. | 2009-06-18 |
|
| To the editor. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. | 2009-06 |
|
| To the editor. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology. | 2009-06 |
|
| Green light from the FDA for new drug development in irritable bowel syndrome and functional dyspepsia. | 2009-06 |
|
| Treatment approaches to irritable bowel syndrome. | 2009-05 |
|
| The use of novel promotility and prosecretory agents for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation. | 2009-05 |
|
| Lubiprostone: trials and tribulations. | 2009-05 |
|
| Lubiprostone stimulates secretion from tracheal submucosal glands of sheep, pigs, and humans. | 2009-05 |
|
| Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon. | 2009-04 |
|
| Lubiprostone: clinical applications beyond constipation. | 2009-03-07 |
|
| Lubiprostone to prevent fecal impaction. | 2009-03 |
|
| Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebo-controlled studies. | 2009-02-01 |
|
| Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects. | 2009-02 |
|
| Lubiprostone: chronic constipation and irritable bowel syndrome with constipation. | 2009-01 |
|
| Constipation: evaluation and treatment of colonic and anorectal motility disorders. | 2009-01 |
|
| Constipation in the elderly: management strategies. | 2009 |
|
| Function and dysfunction of the colon and anorectum in adults: working team report of the Swedish Motility Group (SMoG). | 2009 |
|
| Lubiprostone for constipation and irritable bowel syndrome with constipation. | 2008-12 |
|
| Lubiprostone activates non-CFTR-dependent respiratory epithelial chloride secretion in cystic fibrosis mice. | 2008-11 |
|
| Comparison of the chloride channel activator lubiprostone and the oral laxative Polyethylene Glycol 3350 on mucosal barrier repair in ischemic-injured porcine intestine. | 2008-10-21 |
|
| Cellular mechanisms underlying the laxative effect of flavonol naringenin on rat constipation model. | 2008-10-03 |
|
| [Functional and motor gastrointestinal disorders]. | 2008-10 |
|
| Lubiprostone--a novel treatment for irritable bowel syndrome with constipation. | 2008-09 |
|
| Gateways to clinical trials. | 2008-09 |
|
| FDA approves one drug for irritable bowel syndrome but suspends another. | 2008-08 |
|
| Lubiprostone for chronic idiopathic constipation and irritable bowel syndrome with constipation. | 2008-08 |
|
| Conquering IBS in women: the clinician's pursuit of optimum management strategies. | 2008-07 |
|
| Pharmaceutical approval update. | 2008-06 |
|
| Opioid-induced bowel dysfunction. | 2008-02 |
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
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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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N0000175456
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QA06AX03
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A06AX03
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NBK548000
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C78568
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N0000175573
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CHEMBL1201134
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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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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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METABOLITE ACTIVE -> PARENT |
MAJOR
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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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