Lubiprostone

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Lubiprostone
Lubiprostone.svg
Names
Trade namesAmitiza, others
Other namesRU-0211
SPI-0211
  • 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
Main usesChronic constipation of unknown cause, irritable bowel syndrome associated constipation[1]
Side effectsNausea, diarrhea, abdominal pain, swelling, tiredness[1]
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
use
By mouth
Typical dose8 to 24 mcg BID[1]
External links
AHFS/Drugs.comMonograph
US NLMLubiprostone
MedlinePlusa607034
Legal
License data
Legal status
Pharmacokinetics
BioavailabilityNegligible
Protein binding94%
MetabolismExtensive, CYP not involved
Elimination half-lifeUnknown (lubiprostone)
0.9–1.4 hours (main metabolite)
ExcretionKidney (60%) and fecal (30%)
Chemical and physical data
FormulaC20H32F2O5
Molar mass390.468 g·mol−1
3D model (JSmol)
  • FC(F)(CCCC)[C@]2(O)O[C@@H]1CC(=O)[C@@H]([C@H]1CC2)CCCCCCC(=O)O
  • InChI=1S/C20H32F2O5/c1-2-3-11-19(21,22)20(26)12-10-15-14(16(23)13-17(15)27-20)8-6-4-5-7-9-18(24)25/h14-15,17,26H,2-13H2,1H3,(H,24,25)/t14-,15-,17-,20-/m1/s1 checkY
  • Key:WGFOBBZOWHGYQH-MXHNKVEKSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Lubiprostone, sold under the trade name Amitiza among others, is a medication used to treat chronic constipation of unknown cause and irritable bowel syndrome associated constipation.[1] It is taken by mouth.[1]

Common side effects include nausea, diarrhea, abdominal pain, swelling, and tiredness.[1] Other side effects may include shortness of breath.[1] Safety in pregnancy is unclear.[1] It works by activating certain chloride channels in the intestines which increases fluid release.[1]

Lubiprostone was approved for medical use in the United States in 2006 and Canada in 2015.[1][2] In the United States a month of medication costs about 290 USD as of 2021.[3] It is not commercially available in the United Kingdom.[4]

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.[5]

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.[6]

Dosage

It is used at a dose of 8 mcg twice per day in IBS and 24 mcg twice per day in constipation of unknown cause.[1]

Side effects

Common side event include nausea (31%). Other adverse events (≥5% of patients) included diarrhea (13%), headache (13%), abdominal distension (5%), abdominal pain (5%), flatulence (6%), sinusitis (5%), vomiting (5%), and fecal incontinence (1%).

Contraindications

There is 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 drug tolerance, chemical dependency, or altered serum electrolyte concentration.[7] 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

Cost

The medication is at a cost in the U.S. of $290 (USD) for 60 capsules (8 mcg)[8]

Names

The drug is available in the United States, Japan, Switzerland, India, and Canada.

In Bangladesh and India, lubiprostone is marketed under the trade name Lubigut by Ziska Pharmaceuticals, Lubilax by Beacon Pharmaceuticals, and under the trade name Lubowel by Sun Pharmaceutical.

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 "Lubiprostone Monograph for Professionals". Drugs.com. Retrieved 24 November 2021.
  2. "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 2016-05-04.
  3. "Lubiprostone". Retrieved 24 November 2021.
  4. "Lubiprostone for treating chronic idiopathic constipation | Guidance | NICE". www.nice.org.uk. Retrieved 24 November 2021.
  5. "Amitiza". The American Society of Health-System Pharmacists.
  6. "AMITIZA® (lubiprostone) 8 mcg Now Available to Treat Irritable Bowel Syndrome with Constipation in Adult Women" (Press release). Takeda Pharmaceutical Company. May 26, 2008.
  7. Lacy BE, Levy LC (June 2008). "Lubiprostone: a novel treatment for chronic constipation". Clinical Interventions in Aging. 3 (2): 357–64. doi:10.2147/cia.s2938. PMC 2546479. PMID 18686757.
  8. "Lubiprostone Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 4 April 2021.

External links

Identifiers: