Lubiprostone

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Lubiprostone
Lubiprostone.svg
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
Clinical data
Trade namesAmitiza
AHFS/Drugs.commonograph
MedlinePlusa607034
Licence dataUS FDA:link
Pregnancy cat.C (US)
Legal status-only (US)
RoutesOral
Pharmacokinetic data
BioavailabilityNegligible
Protein binding94%
MetabolismExtensive, CYP not involved
Half-lifeUnknown (lubiprostone)
0.9–1.4 hours (main metabolite)
ExcretionRenal (60%) and fecal (30%)
Identifiers
CAS number136790-76-6 YesY
ATC codeA06AX03
PubChemCID 157920
DrugBankDB01046
ChemSpider138948 YesY
UNII7662KG2R6K YesY
KEGGD04790 YesY
ChEMBLCHEMBL1201134 N
SynonymsAmitiza
RU-0211
SPI-0211
Chemical data
FormulaC20H32F2O5 
Mol. mass390.462 g/mol
 N (what is this?)  (verify)
 
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Lubiprostone
Lubiprostone.svg
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
Clinical data
Trade namesAmitiza
AHFS/Drugs.commonograph
MedlinePlusa607034
Licence dataUS FDA:link
Pregnancy cat.C (US)
Legal status-only (US)
RoutesOral
Pharmacokinetic data
BioavailabilityNegligible
Protein binding94%
MetabolismExtensive, CYP not involved
Half-lifeUnknown (lubiprostone)
0.9–1.4 hours (main metabolite)
ExcretionRenal (60%) and fecal (30%)
Identifiers
CAS number136790-76-6 YesY
ATC codeA06AX03
PubChemCID 157920
DrugBankDB01046
ChemSpider138948 YesY
UNII7662KG2R6K YesY
KEGGD04790 YesY
ChEMBLCHEMBL1201134 N
SynonymsAmitiza
RU-0211
SPI-0211
Chemical data
FormulaC20H32F2O5 
Mol. mass390.462 g/mol
 N (what is this?)  (verify)

Lubiprostone (rINN, marketed under the trade name Amitiza) 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.

Medical uses[edit]

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.[1]

Lubiprostone 24 mcg capsules twice daily is approved to treat chronic idiopathic constipation (CIC) in adults.

Lubiprostone 24 mcg twice daily 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 8 mcg capsules twice daily is approved to treat irritable bowel syndrome with constipation (IBS-C) in women 18 years of age and older.

As of 20 July 2006, lubiprostone has not been studied in children.[needs update] There is current research underway to determine the safety and efficacy in postoperative bowel dysfunction.

Adverse effects[edit]

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%).

Contraindications[edit]

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[edit]

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[edit]

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.

Chemistry[edit]

A laboratory synthesis of lubiprostone has been reported:[2]

Lubiprostone.png

Legal status[edit]

Lubiprostone received approval from the Food and Drug Administration in 2008 to treat irritable bowel syndrome with constipation (IBS-C). It is available through prescription only.

References[edit]

  1. ^ "amitiza". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  2. ^ Sobrera, L. A.; Castaner, J. (2004). Drugs of the Future 29 (4): 336. 

External links[edit]