Lubiprostone
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| 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 |
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| Clinical data | |
| Trade names | Amitiza |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a607034 |
| Licence data | US FDA:link |
| Pregnancy cat. | C (US) |
| Legal status | ℞-only (US) |
| 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 | 136790-76-6  |
| ATC code | A06AX03 |
| PubChem | CID 157920 |
| DrugBank | APRD01298 |
| ChemSpider | 138948 |
| UNII | 7662KG2R6K |
| KEGG | D04790 |
| ChEMBL | CHEMBL1201134  |
| Synonyms | Amitiza RU-0211 SPI-0211 |
| Chemical data | |
| Formula | C20H32F2O5 |
| Mol. mass | 390.462 g/mol |
| SMILES | eMolecules & PubChem |
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Lubiprostone (rINN, marketed under the trade name Amitiza) is a medication used in the management of chronic idiopathic constipation and irritable bowel syndrome. It was approved by the U.S. Food and Drug Administration (FDA) for this purpose on 31 January 2006.
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[edit] Medical uses
Lubiprostone is used for the treatment of chronic constipation of unknown cause and irritable bowel syndrome associated with constipation.[1]
As of 20 July 2006, Lubiprostone had not been studied in children. There is current research underway to determine the efficacy in postoperative bowel dysfunction, and opioid-induced bowel dysfunction.
[edit] 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%).
[edit] 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.
Lubiprostone is contraindicated in patients exhibiting chronic diarrhea, bowel obstruction, or diarrhea-predominant irritable bowel syndrome.
[edit] 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.
[edit] 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.
[edit] Chemistry
Synthesis:[2]
[edit] Legal status
Lubiprostone received approval from the Food and Drug Administration on 29 April 2008 to treat irritable bowel syndrome with constipation (IBS-C).
[edit] References
- ^ "amitiza". The American Society of Health-System Pharmacists. http://www.drugs.com/monograph/amitiza.html. Retrieved 3 April 2011.
- ^ Sobrera, L. A.; Castaner, J. (2004). Drugs of the Future 29 (4): 336.
- Katzung, B.G. (2007). Basic and Clinical Pharmacology, 10th edition. McGraw-Hill.
- "Clinical Pharmacology Online Database". http://www.clinicalpharmacology.com/default.asp. Retrieved 2007-02-28.[dead link]
[edit] External links
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