Lubiprostone

Names
Trade names	Amitiza, others
Other names	RU-0211 SPI-0211
IUPAC name 7-[(1R,3R,6R,7R)-3-(1,1-Difluoropentyl)-3-hydroxy-8-oxo-2-oxabicyclo[4.3.0]non-7-yl]heptanoic acid
Clinical data
Main uses	Chronic constipation of unknown cause,irritable bowel syndrome associated constipation[1]
Side effects	Nausea, diarrhea, abdominal pain, swelling, tiredness[1]
Pregnancy category	US: C (Risk not ruled out)
Routes of use	By mouth
Typical dose	8 to 24 mcg BID[1]
External links
AHFS/Drugs.com	Monograph
MedlinePlus	a607034
Legal
License data	US FDA: Lubiprostone
Legal status	US: ℞-only
Pharmacokinetics
Bioavailability	Negligible
Protein binding	94%
Metabolism	Extensive,CYP not involved
Eliminationhalf-life	Unknown (lubiprostone) 0.9–1.4 hours (main metabolite)
Excretion	Kidney (60%) and fecal (30%)
Chemical and physical data
Formula	C20H32F2O5
Molar mass	390.468 g·mol−1
3D model (JSmol)	Interactive image
SMILES FC(F)(CCCC)[C@]2(O)O[C@@H]1CC(=O)[C@@H]([C@H]1CC2)CCCCCCC(=O)O
InChI 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 Y Key:WGFOBBZOWHGYQH-MXHNKVEKSA-N Y

Lubiprostone, sold under the trade nameAmitiza among others, is a medication used to treatchronic constipation of unknown cause andirritable bowel syndrome associated constipation.^[1] It is taken by mouth.^[1]

Common side effects include nausea, diarrhea, abdominal pain, swelling, and tiredness.^[1] Other side effects may include shortness of breath.^[1] Safety in pregnancy is unclear.^[1] It works by activating certainchloride channels in theintestines which increases fluid release.^[1]

Lubiprostone was approved for medical use in the United States in 2006 and Canada in 2015.^[1][2] In the United States a month of medication costs about 290 USD as of 2021.^[3] A generic version was approved in 2021 in the USA.^[4] It is not commercially available in the United Kingdom.^[5]

Medical uses

Lubiprostone is used for the treatment of chronicconstipation of unknown cause in adults, as well asirritable bowel syndrome associated with constipation in women.^[6]

Lubiprostone is approved to treat chronic idiopathic constipation (CIC) in adults.

Lubiprostone is also approved to treatopioid-induced constipation, in adults with chronic non-cancer pain. The effectiveness of lubiprostone has not been established in patients who are taking a diphenylheptane opioid (e.g., methadone).

Lubiprostone is approved to treat irritable bowel syndrome with constipation (IBS-C) in women 18 years of age and older.^[7]

Dosage

It is used at a dose of 8 mcg twice per day in IBS and 24 mcg twice per day in constipation of unknown cause.^[1]

Side effects

Common side event includenausea (31%). Other adverse events (≥5% of patients) includeddiarrhea (13%),headache (13%),abdominal distension (5%),abdominal pain (5%),flatulence (6%),sinusitis (5%),vomiting (5%), andfecal incontinence (1%).

Contraindications

There is no current data on use in people with liver or kidney complications. The effects on pregnancy have not been studied in humans but testing inguinea pigs resulted in fetal loss.

Amitiza is not approved for use in children. Lubiprostone is contraindicated in patients exhibiting chronicdiarrhea,bowel obstruction, or diarrhea-predominantirritable bowel syndrome.

Mechanism of action

Lubiprostone is a bicyclicfatty acid derived fromprostaglandin E1 that acts by specifically activatingClC-2 chloride channels on the apical aspect of gastrointestinalepithelial cells, producing a chloride-rich fluid secretion. These secretions soften the stool, increase motility, and promote spontaneous bowel movements (SBM).

Symptoms of constipation such as pain and bloating are usually improved within one week, and SBM may occur within one day.

Pharmacokinetics

Unlike manylaxative products, lubiprostone does not show signs ofdrug tolerance,chemical dependency, or altered serumelectrolyte concentration.^[8] There was no rebound effect following withdrawal of treatment, but a gradual return to pre-treatment bowel movement frequency should be expected.

Minimal distribution of the drug occurs beyond the immediate gastrointestinal tissues. Lubiprostone is rapidly metabolized byreduction/oxidation, mediated by carbonyl reductase. There is no metabolic involvement of the hepaticcytochrome P450 system. The measurable metabolite, M3, exists in very low levels in plasma and makes up less than 10% of the total administered dose.

Data indicate that metabolism occurs locally in thestomach andjejunum.

Society and culture

Cost

The medication is at a cost in the U.S. of $290 (USD) for 60 capsules (8 mcg)^[9]

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  Lubiprostone costs (US)

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  Lubiprostone prescriptions (US)

Names

The drug is available in the United States, Japan, Switzerland, India, and Canada.

InBangladesh andIndia, lubiprostone is marketed under the trade name Lubigut byZiska Pharmaceuticals, Lubilax byBeacon Pharmaceuticals, and under the trade name Lubowel bySun Pharmaceutical.

References

External links

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