Lubiprostone

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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
Identifiers
CAS number	136790-76-6
ATC code	?
PubChem	157920
DrugBank	APRD01298
Chemical data
Formula	C20H32F2O5
Mol. mass	390.462 g/mol
SMILES	eMolecules & PubChem
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	US
Pregnancy cat.	C(US)
Legal status	℞-only(US)
Routes	Oral

Lubiprostone (rINN, marketed under the trade name Amitiza) is a medication used in the management of idiopathic chronic constipation. It was approved by the U.S. Food and Drug Administration for this purpose on January 31, 2006.

Contents 1 Indications 2 Mode of action 3 Pharmacokinetics 4 Side effects 5 Contraindications 6 References

[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.

Lubiprostone was submitted on July 12, 2007 to the United States Food and Drug Administration (FDA) as a New Drug Application to treat Irritable Bowel Syndrome with constipation (IBS-C).

[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 indicate that metabolism occurs locally in the stomach and jejunum.

[edit] Side 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 (7%), abdominal pain (7%), flatulence (6%), sinusitis (5%) and vomiting (5%).

[edit] Contraindications

There are no current data on use in patients with hepatic and/or renal 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 or GI obstruction.

[edit] References