Lubiprostone

Lubiprostone (rINN, marketed under the trade name Amitiza among others) is a medication used in the management of chronic idiopathic constipation, predominantly irritable bowel syndrome-associated constipation in women and opioid-induced constipation.

Lubiprostone
Clinical data
Trade namesAmitiza
Other namesAmitiza
RU-0211
SPI-0211
AHFS/Drugs.comMonograph
MedlinePlusa607034
License data
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		Oral
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    BioavailabilityNegligible
    Protein binding94%
    MetabolismExtensive, CYP not involved
    Elimination half-lifeUnknown (lubiprostone)
    0.9–1.4 hours (main metabolite)
    ExcretionRenal (60%) and fecal (30%)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.107.168
    Chemical and physical data
    FormulaC20H32F2O5
    Molar mass390.462 g/mol g·mol−1
    3D model (JSmol)
     NY (what is this?)  (verify)

    It was initially approved by the U.S. Food and Drug Administration (FDA) in 2006 and recommended for use in the UK by the National Institute for Health and Care Excellence (NICE) in 2014.[1] It is expensive as of 2017, with the cost to the NHS being £29.68 per 24 mg 28-cap pack as of April 2017.[2]

    Medical uses

    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.[3]

    Lubiprostone is approved to treat chronic idiopathic constipation (CIC) in adults.

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

    As of 12 November 2014, lubiprostone has not been studied in children. There is current research under way to determine the safety and efficacy in postoperative bowel dysfunction.

    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%) vomiting (5%) and fecal incontinence (1%).

    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. 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

    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

    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.

    Society and culture

    Lubiprostone received approval from the Food and Drug Administration in 2008 to treat irritable bowel syndrome with constipation (IBS-C) and is available through prescription only. As of 2014, the drug is available in the United States, Japan, Switzerland, India and the United Kingdom; review by Health Canada began in late 2014.[4]

    Brand names

    In Bangladesh and India, lubiprostone is marketed under the trade name Lubilax by Beacon Pharmaceuticals Limited, and under the trade name Lubowel by SunPharma.

    References
    1. "Lubiprostone for treating chronic idiopathic constipation - Technology appraisal guidance [TA318]". NICE. 23 July 2014. Retrieved 13 April 2017.
    2. "LUBIPROSTONE - Other drugs used in constipation". British National Formulary. 2014. Retrieved 13 April 2017.
    3. "Amitiza". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
    4. House, Douglas W. (31 December 2014). "Canada accepts Sucampo's NDS for constipation med". Seeking Alpha.
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