Lubiprostone

drugbox
IUPAC_name = 7- [(1"R",3"R",6"R",7"R")-3-(1,1-difluoropentyl)-3-hydroxy-
8-oxo-2-oxabicyclo [4.3.0] non-7-yl] heptanoic acid

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width = 280
CAS_number = 136790-76-6
ATC_prefix = A06
ATC_suffix = AX03
PubChem = 157920
DrugBank = APRD01298
C = 20 | H = 32 | F = 2 | O = 5
molecular_weight = 390.462 g/mol
bioavailability = Negligible
protein_bound = 94%
smiles = CCCCC(C1(CCC2C(O1)CC(=O)C2CCCCCCC(=O)O)O)(F)F
synonyms = Amitiza
RU-0211
SPI-0211
metabolism = Extensive, CYP not involved
elimination_half-life = Unknown (lubiprostone)
0.9–1.4 hours (main metabolite)
excretion = Renal (60%) and fecal (30%)
licence_US = Lubiprostone
pregnancy_US = C
legal_US = Rx-only
routes_of_administration = 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.

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 received approval from the United States Food and Drug Administration (FDA) on 04/29/2008 to treat Irritable Bowel Syndrome with constipation (IBS-C).

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 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 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.

ide 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%).

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.

References

#cite book | last = Katzung | first = B.G. | title = Basic and Clinical Pharmacology, 10th edition | publisher = McGraw-Hill | date = 2007
#cite web | title = Clinical Pharmacology Online Database | url = http://www.clinicalpharmacology.com/default.asp | accessdate = 2007-02-28