Lubiprostone
Systematic (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
Trade names Amitiza
AHFS/Drugs.com
MedlinePlus
Licence data US FDA:
Pregnancy cat.
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability Negligible
Protein binding 94%
Metabolism Extensive, CYP not involved
Half-life Unknown (lubiprostone)
0.9–1.4 hours (main metabolite)
Excretion Renal (60%) and fecal (30%)
Identifiers
CAS number  YesY
ATC code A06
PubChem
DrugBank
ChemSpider  YesY
UNII  YesY
KEGG  YesY
ChEMBL  N
Synonyms Amitiza
RU-0211
SPI-0211
Chemical data
Formula C20H32F2O5 
Mol. mass 390.462 g/mol
 N   

Lubiprostone (rINN, marketed under the trade name Amitiza) is a medication used in the management of chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation. It was initially approved by the U.S. Food and Drug Administration (FDA) in 2006.

Medical uses

Lubiprostone is used for the treatment of chronic constipation of unknown cause in adults, as well as irritable bowel syndrome associated with constipation in women.[1]

Lubiprostone 24 mcg capsules twice daily is approved to treat chronic idiopathic constipation (CIC) in adults.

Lubiprostone 24 mcg twice daily is also approved to treat opioid-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 8 mcg capsules twice daily is approved to treat irritable bowel syndrome with constipation (IBS-C) in women 18 years of age and older.

As of 12 November 2014, lubiprostone has not been studied in children. There is current research underway to determine the safety and efficacy in postoperative bowel dysfunction.

Adverse effects

In clinical trials, the most common adverse event was nausea (31%). Other adverse events (≥5% of patients) included diarrhea (13%), headache (13%), abdominal distention (5%), abdominal pain (5%), flatulence (6%), sinusitis (5%) and vomiting (5%).

Contraindications

There are no current data on use in people with liver or kidney complications. The effects on pregnancy have not been studied in humans but testing in Guinea pigs resulted in fetal loss. Amitiza is not approved for use in children. Lubiprostone is contraindicated in patients exhibiting chronic diarrhea, bowel obstruction, or diarrhea-predominant irritable bowel syndrome.

Mechanism of action

Lubiprostone is a bicyclic fatty acid derived from prostaglandin E1 that 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).

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

Pharmacokinetics

Unlike many laxative products, lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte concentration. 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 by reduction/oxidation, mediated by carbonyl reductase. There is no metabolic involvement of the hepatic cytochrome 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 the stomach and jejunum.

Chemistry

A laboratory synthesis of lubiprostone has been reported:[2]

Legal status

Lubiprostone received approval from the Food and Drug Administration in 2008 to treat irritable bowel syndrome with constipation (IBS-C). It is available through prescription only.

References

  1. ^ "amitiza". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  2. ^ Sobrera, L. A.; Castaner, J. (2004). Drugs of the Future 29 (4): 336. 

External links

  • Official Website