Lubiprostone
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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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| Identifiers | |
| CAS number | |
| ATC code | ? |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C20H32F2O5 |
| Mol. mass | 390.462 g/mol |
| SMILES | search in , |
| Synonyms | Amitiza RU-0211 SPI-0211 |
| 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%) |
| Therapeutic considerations | |
| Licence data |
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| Pregnancy cat. |
C(US) |
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| Routes | Oral |
Lubiprostone (rINN, marketed under the trade name Amitiza) is a medication used in the management of chronic constipation. It was approved by the U.S. Food and Drug Administration for this purpose on January 31, 2006.
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[edit] Indications
Lubiprostone is a gastrointestinal agent used for the treatment of idiopathic chronic constipation. It is well-tolerated in adults, including elderly patients. As of July 20, 2006, Lubiprostone had not been studied in pediatric patients.
There is current research underway to determine the efficacy of Lubiprostone in patients with constipation-predominant IBS, postoperative bowel dysfunction, and opioid-induced bowel dysfunction.
[edit] Mode of action
Lubiprostone 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).
Symptoms of constipation (pain, bloating) are usually observed 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 GI 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 indicates that metabolism occurs locally in the stomach and jejunum.
[edit] Contraindications
There is no current data on use in patients with hepatic and/or renal complications. The effects on pregnancy have not been studied.
Lubipristone is contraindicated in patients exhibiting chronic diarrhea or GI obstruction.
[edit] References
- Katzung, B.G. (2007). Basic and Clinical Pharmacology, 10th edition. McGraw-Hill.
- Clinical Pharmacology Online Database. Retrieved on 2007-02-28.
