Lubiprostone
Encyclopedia
Lubiprostone is a medication
used in the management of chronic
idiopathic
constipation
and irritable bowel syndrome
. It was approved by the U.S. Food and Drug Administration
(FDA) for this purpose on 31 January 2006.
of unknown cause and irritable bowel syndrome
associated with constipation.
As of 20 July 2006, Lubiprostone had not been studied in children. There is current research underway to determine the efficacy in postoperative bowel dysfunction, and opioid
-induced bowel dysfunction.
Lubiprostone is contraindicated in patients exhibiting chronic diarrhea
, bowel obstruction
, or diarrhea-predominant irritable bowel syndrome.
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.
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
.
(IBS-C).
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
used in the management of chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
and irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
. It was approved by the U.S. Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) for this purpose on 31 January 2006.
Medical uses
Lubiprostone is used for the treatment of chronic constipationConstipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
of unknown cause and irritable bowel syndrome
Irritable bowel syndrome
Irritable bowel syndrome is a diagnosis of exclusion. It is a functional bowel disorder characterized by chronic abdominal pain, discomfort, bloating, and alteration of bowel habits in the absence of any detectable organic cause. In some cases, the symptoms are relieved by bowel movements...
associated with constipation.
As of 20 July 2006, Lubiprostone had not been studied in children. There is current research underway to determine the efficacy in postoperative bowel dysfunction, and opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
-induced 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%) and vomiting (5%).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.Lubiprostone is contraindicated in patients exhibiting chronic diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, bowel obstruction
Bowel obstruction
Bowel obstruction is a mechanical or functional obstruction of the intestines, preventing the normal transit of the products of digestion. It can occur at any level distal to the duodenum of the small intestine and is a medical emergency...
, or diarrhea-predominant irritable bowel syndrome.
Mechanism of action
Lubiprostone is a bicyclic fatty acidFatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
derived from prostaglandin E1
Prostaglandin E1
Prostaglandin E1 , known pharmaceutically as alprostadil, is a prostaglandin. It is a drug used in the treatment of erectile dysfunction and has vasodilatory properties.-Sexual dysfunction:...
that acts by specifically activating ClC-2 chloride channels
CLCN2
Chloride channel protein 2 is a protein that in humans is encoded by the CLCN2 gene. Mutations of this gene have been found to cause Idiopathic generalised epilepsy . CLCN2 contains a transmembrane region that is involved in chloride ion transport as well two intracellular copies of the CBS domain....
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 laxativeLaxative
Laxatives are foods, compounds, or drugs taken to induce bowel movements or to loosen the stool, most often taken to treat constipation. Certain stimulant, lubricant, and saline laxatives are used to evacuate the colon for rectal and/or bowel examinations, and may be supplemented by enemas under...
products, Lubiprostone does not show signs of tolerance, dependency, or altered serum electrolyte
Electrolyte
In chemistry, an electrolyte is any substance containing free ions that make the substance electrically conductive. The most typical electrolyte is an ionic solution, but molten electrolytes and solid electrolytes are also possible....
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
Redox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
/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
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
and jejunum
Jejunum
The jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...
.
Legal status
Lubiprostone received approval from the Food and Drug Administration on 29 April 2008 to treat irritable bowel syndrome with constipationConstipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
(IBS-C).