Lubiprostone
Systematic (IUPAC) name | |
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7-[(1R,3R,6R,7R)-3-(1,1-Difluoropentyl)-3-hydroxy-8-oxo-2-oxabicyclo[4.3.0]non-7-yl]heptanoic acid
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Clinical data | |
Trade names | Amitiza |
AHFS/Drugs.com | monograph |
MedlinePlus | a607034 |
Licence data | US FDA:link |
Pregnancy category |
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Legal status |
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Routes of administration |
Oral |
Pharmacokinetic data | |
Bioavailability | Negligible |
Protein binding | 94% |
Metabolism | Extensive, CYP not involved |
Biological half-life | Unknown (lubiprostone) 0.9–1.4 hours (main metabolite) |
Excretion | Renal (60%) and fecal (30%) |
Identifiers | |
CAS Number | 136790-76-6 |
ATC code | A06AX03 (WHO) |
PubChem | CID: 157920 |
IUPHAR/BPS | 4242 |
DrugBank | DB01046 |
ChemSpider | 138948 |
UNII | 7662KG2R6K |
KEGG | D04790 |
ChEMBL | CHEMBL1201134 |
Synonyms | Amitiza RU-0211 SPI-0211 |
Chemical data | |
Formula | C20H32F2O5 |
Molecular mass | 390.462 g/mol |
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Lubiprostone (rINN, marketed under the trade name Amitiza among others) 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. It is very expensive as of 2012.[1]
Contents
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.[2]
Lubiprostone is approved to treat chronic idiopathic constipation (CIC) in adults.
Lubiprostone 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 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%) Vomiting (5%) and Fecal Incontinence (1%).
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.
Society and culture
Legal status
Lubiprostone received approval from the Food and Drug Administration in 2008 to treat irritable bowel syndrome with constipation (IBS-C) and is available through prescription only. As of 2014[update], the drug is available in the United States, Japan, Switzerland and the United Kingdom; review by Health Canada began in late 2014.[3]
Brand names
In Bangladesh under the trade name Lubilax marketed by Beacon Pharmaceuticals Limited
References
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External links
- Chemical articles having calculated molecular weight overwritten
- Infobox drug articles without a structure image
- Articles containing potentially dated statements from 2014
- Articles with dead external links from October 2010
- Drugs acting on the gastrointestinal system and metabolism
- Fatty acids
- Laxatives
- Organofluorides
- Alcohols
- Ketones