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

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
Structure of LUBIPROSTONE

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

HIDE SMILES / InChI

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

Description
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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Amitiza

Approved Use

Amitiza 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 Date

2006
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
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

AUC

ValueDoseCo-administeredAnalytePopulation
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

T1/2

ValueDoseCo-administeredAnalytePopulation
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

Funbound

ValueDoseCo-administeredAnalytePopulation
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

Doses

DosePopulationAdverse 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%)
Dyspnea (2%)
Sources: Page: p.1, 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
Other AEs: Nausea, Diarrhea...
Other AEs:
Nausea (45%)
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%)
Sources: Page: p.8
AEs

AEs

AESignificanceDosePopulation
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

OverviewOther

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
likely
no
no
no
no
no
no
no
no
no
no
no
no
no
no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Lubiprostone: a new drug for the treatment of chronic idiopathic constipation.
2007 Fall
Update on the management of adults with chronic idiopathic constipation.
2007 Jun
Gateways to clinical trials.
2007 Nov
Lubiprostone: a novel treatment for chronic constipation.
2008
Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation.
2008 Apr
Lubiprostone for chronic idiopathic constipation and irritable bowel syndrome with constipation.
2008 Aug
Clinical pharmacology of lubiprostone, a chloride channel activator in defecation disorders.
2008 Aug
A synthetic prostone activates apical chloride channels in A6 epithelial cells.
2008 Aug
Lubiprostone for constipation and irritable bowel syndrome with constipation.
2008 Dec
Opioid-induced bowel dysfunction.
2008 Feb
Lubiprostone: easing the strain of constipation?
2008 Jan
Conquering IBS in women: the clinician's pursuit of optimum management strategies.
2008 Jul
The Food and Drug Administration approves lubiprostone for irritable bowel syndrome with constipation.
2008 Jul
Effects of lubiprostone on human uterine smooth muscle cells.
2008 Jun
Development of drugs for gastrointestinal motor disorders: translating science to clinical need.
2008 Mar
Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach and colon.
2008 May
[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
Lubiprostone--a novel treatment for irritable bowel syndrome with constipation.
2008 Sep
Gateways to clinical trials.
2008 Sep
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
Management of constipation in the elderly: emerging therapeutic strategies.
2008 Sep 7
Constipation in the elderly: management strategies.
2009
The FDA and IBS drug development.
2009 Dec
Effect of a chloride channel activator, lubiprostone, on colonic sensory and motor functions in healthy subjects.
2009 Feb
Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome--results of two randomized, placebo-controlled studies.
2009 Feb 1
Lubiprostone: chronic constipation and irritable bowel syndrome with constipation.
2009 Jan
Pathogenesis and management of irritable bowel syndrome.
2009 Jan-Mar
A 73-year-old man with long-term immobility presenting with abdominal pain.
2009 Jul 14
To the editor. CLC chloride channels and transporters: from genes to protein structure, pathology and physiology.
2009 Jun
Green light from the FDA for new drug development in irritable bowel syndrome and functional dyspepsia.
2009 Jun
Lubiprostone: in constipation-predominant irritable bowel syndrome.
2009 Jun 18
Treatment approaches to irritable bowel syndrome.
2009 May
The use of novel promotility and prosecretory agents for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation.
2009 May
Lubiprostone: trials and tribulations.
2009 May
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
Management of irritable bowel syndrome.
2009 Sep
Activation of intestinal Cl- secretion by lubiprostone requires the cystic fibrosis transmembrane conductance regulator.
2009 Sep
Update on the management of constipation in the elderly: new treatment options.
2010 Aug 9
Review article: new receptor targets for medical therapy in irritable bowel syndrome.
2010 Jan
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
Patents

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
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 Sat Dec 16 16:45:42 GMT 2023
Edited
by admin
on Sat Dec 16 16:45:42 GMT 2023
Record UNII
7662KG2R6K
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LUBIPROSTONE
INN   JAN   MART.   MI   ORANGE BOOK   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
AMITIZA
Brand Name English
LUBIPROSTONE [JAN]
Common Name English
RU-0211
Code English
lubiprostone [INN]
Common Name English
Lubiprostone [WHO-DD]
Common Name English
7-[(2R,4aR,5R,7aR)-2-(1,1-Difluoropentyl)-2-hydroxy-6-oxooctahydrocyclopenta[b]pyran-5-yl]heptanoic acid
Systematic Name English
LUBIPROSTONE [USAN]
Common Name English
(-)-7-((2R,4AR,5R,7AR)-2-(1,1-DIFLUOROPENTYL)-2-HYDROXY-6-OXOOCTAHYDROCYCLOPENTA(B)PYRAN-5-YL)HEPTANOIC ACID
Common Name English
LUBIPROSTONE [VANDF]
Common Name English
LUBIPROSTONE [ORANGE BOOK]
Common Name English
LUBIPROSTONE [MI]
Common Name English
PROSTAN-1-OIC ACID, 16,16-DIFLUORO-11-HYDROXY-9,15-DIOXO-, (11.ALPHA.)-
Common Name English
LUBIPROSTONE [MART.]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175456
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
WHO-VATC QA06AX03
Created by admin on Sat Dec 16 16:45:43 GMT 2023 , Edited by admin on Sat Dec 16 16:45:43 GMT 2023
WHO-ATC A06AX03
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
LIVERTOX NBK548000
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
NCI_THESAURUS C78568
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
NDF-RT N0000175573
Created by admin on Sat Dec 16 16:45:43 GMT 2023 , Edited by admin on Sat Dec 16 16:45:43 GMT 2023
Code System Code Type Description
SMS_ID
100000124449
Created by admin on Sat Dec 16 16:45:43 GMT 2023 , Edited by admin on Sat Dec 16 16:45:43 GMT 2023
PRIMARY
ChEMBL
CHEMBL1201134
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
PUBCHEM
157920
Created by admin on Sat Dec 16 16:45:43 GMT 2023 , Edited by admin on Sat Dec 16 16:45:43 GMT 2023
PRIMARY
MERCK INDEX
m6919
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY Merck Index
DAILYMED
7662KG2R6K
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
INN
8254
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
RXCUI
623033
Created by admin on Sat Dec 16 16:45:43 GMT 2023 , Edited by admin on Sat Dec 16 16:45:43 GMT 2023
PRIMARY RxNorm
WIKIPEDIA
Lubiprostone
Created by admin on Sat Dec 16 16:45:43 GMT 2023 , Edited by admin on Sat Dec 16 16:45:43 GMT 2023
PRIMARY
DRUG CENTRAL
4123
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
DRUG BANK
DB01046
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
MESH
C506401
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
IUPHAR
4242
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
CAS
333963-40-9
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
ALTERNATIVE
FDA UNII
7662KG2R6K
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
EVMPD
SUB32077
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
EPA CompTox
DTXSID5048639
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
USAN
NN-66
Created by admin on Sat Dec 16 16:45:43 GMT 2023 , Edited by admin on Sat Dec 16 16:45:43 GMT 2023
PRIMARY
NCI_THESAURUS
C66040
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
LACTMED
Lubiprostone
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
CAS
136790-76-6
Created by admin on Sat Dec 16 16:45:42 GMT 2023 , Edited by admin on Sat Dec 16 16:45:42 GMT 2023
PRIMARY
Related Record Type Details
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.
PARENT -> DERIVATIVE
BINDER->LIGAND
BINDING
TARGET -> ACTIVATOR
Related Record Type Details
METABOLITE ACTIVE -> PARENT
MAJOR
PLASMA
METABOLITE -> PARENT
MAJOR
PLASMA
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC