SeHCAT

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SeHCAT
Tauroselcholic acid.svg
Names
IUPAC name
(75Se)-2-[[[[(3α,5α,7α,12α,20S)-3,7,12-trihydroxy-20-methylpregnan-21-yl]seleno]acetyl]amino]ethanesulfonic acid,
Other names
23-Seleno-25-homo-tauro-cholic acid; Selenium homocholic acid taurine; Tauroselcholic acid
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
UNII
  • InChI=1S/C26H45NO7SSe/c1-15(13-36-14-23(31)27-8-9-35(32,33)34)18-4-5-19-24-20(12-22(30)26(18,19)3)25(2)7-6-17(28)10-16(25)11-21(24)29/h15-22,24,28-30H,4-14H2,1-3H3,(H,27,31)(H,32,33,34)/t15-,16+,17-,18-,19+,20+,21-,22+,24+,25+,26-/m1/s1 Yes check.svgY
    Key: JCMLWGQJPSGGEI-HZAMXZRMSA-N Yes check.svgY
  • C[C@H](C[75Se]CC(NCCS(O)(=O)=O)=O)[C@@]1([H])CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@]4([H])C[C@H](O)CC[C@]4(C)[C@@]3([H])C[C@H](O)[C@@]21C
Properties
C26H45NO7SSe
Molar mass 594.68 g·mol−1
Pharmacology
V09DX01 ( WHO )
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

SeHCAT (23-seleno-25-homotaurocholic acid, selenium homocholic acid taurine, or tauroselcholic acid) is a drug used in a clinical test to diagnose bile acid malabsorption. [1]

Development

SeHCAT is a taurine-conjugated bile acid analog which was synthesized for use as a radiopharmaceutical to investigate in vivo the enterohepatic circulation of bile salts. [2] By incorporating the gamma-emitter 75Se into the SeHCAT molecule, the retention in the body or the loss of this compound into the feces could be studied easily using a standard gamma camera, available in most clinical nuclear medicine departments.[ citation needed ]

SeHCAT has been shown to be absorbed from the gut and excreted into the bile at the same rate as cholic acid, one of the major natural bile acids in humans. It undergoes secretion into the biliary tree, gallbladder and intestine in response to food, and is reabsorbed efficiently in the ileum, with kinetics similar to natural bile acids. [2] [3] It was soon shown to be the most convenient and accurate method available to assess and measure bile acid turnover in the intestine. [4] SeHCAT testing was commercially developed by Amersham International Ltd (Amersham plc is now part of GE Healthcare Medical Diagnostics division) for clinical use to investigate malabsorption in patients with diarrhea. This test has replaced 14C-labeled glycocholic acid (or taurocholic acid) breath tests and fecal bile acid measurements, which now have no place in the routine clinical investigation of malabsorption.[ citation needed ]

Procedure

A capsule containing radiolabelled 75SeHCAT (with 370 kBq of Selenium-75 and less than 0.1 mg SeHCAT) is taken orally with water, to ensure passage of the capsule into the gastrointestinal tract. The physical half life of 75Se is approximately 118 days; activity is adjusted to a standard reference date.[ citation needed ]

Patients may be given instructions to fast prior to capsule administration; there is significant variation in clinical practice in this regard. [5] The effective dose of radiation for an adult given 370 kBq of SeHCAT is 0.26 mSv. [6] (For comparison, the radiation exposure from an abdominal CT scan is quoted at 5.3 mSv and annual background exposure in the UK 1-3 mSv. [7] ) Measurements were originally performed with a whole-body counter but are usually performed now with an uncollimated gamma camera. The patient is scanned supine or prone with anterior and posterior acquisition from head to thigh 1 to 3 hours after taking the capsule. Scanning is repeated after 7 days. Background values are subtracted and care must be taken to avoid external sources of radiation in a nuclear medicine department.

From these measurements, the percent retention of SeHCAT at 7 days is calculated. A 7-day SeHCAT retention value greater than 15% is considered to be normal, with values less than 15% signifying excessive bile acid loss, as found in bile acid malabsorption.

With more frequent measurements, it is possible to calculate SeHCAT retention whole-body half-life; this is not routinely measured in a clinical setting. A half-life of greater than 2.8 days has been quoted as normal. [8]

Clinical use

The SeHCAT test is used to investigate patients with suspected bile acid malabsorption, who usually experience chronic diarrhea, often passing watery feces 5 to 10 times each day. When ileum has been removed following surgery, or is inflamed in Crohn's disease, the 7-day SeHCAT retention usually is abnormal, and most of these patients will benefit from treatment with bile acid sequestrants. [9] [10] The enterohepatic circulation of bile acids is reduced in these patients with ileal abnormalities and, as the normal bile acid retention exceeds 95%, only a small degree of change is needed. Bile acid malabsorption can also be secondary to cholecystectomy, vagotomy and other disorders affecting intestinal motility or digestion such as radiation enteritis, celiac disease, and small intestinal bacterial overgrowth.[ citation needed ]

A similar picture of chronic diarrhea, an abnormal SeHCAT retention and a response to bile acid sequestrants, in the absence of other disorders of the intestine, is characteristic of idiopathic bile acid malabsorption – also called primary bile acid diarrhea. These patients are frequently misdiagnosed as having the irritable bowel syndrome, as clinicians fail to recognize the condition, do not think of performing a SeHCAT test, or do not have it available. [11]

There have been at least 18 studies of the use of SeHCAT testing in diarrhea-predominant irritable bowel syndrome patients. When these data were combined, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a bile acid sequestrant. [12]

Related Research Articles

<span class="mw-page-title-main">Diarrhea</span> Loose or liquid bowel movements

Diarrhea, also spelled diarrhoea or diarrhœa in British English, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin with loss of the normal stretchiness of the skin and irritable behaviour. This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe. Loose but non-watery stools in babies who are exclusively breastfed, however, are normal.

<span class="mw-page-title-main">Irritable bowel syndrome</span> Functional gastrointestinal disorder

Irritable bowel syndrome (IBS) is a "disorder of gut-brain interaction" characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating and changes in the consistency of bowel movements. These symptoms may occur over a long time, sometimes for years. IBS can negatively affect quality of life and may result in missed school or work or reduced productivity at work. Disorders such as anxiety, major depression, and chronic fatigue syndrome are common among people with IBS.

The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption from the gut. In general, they are classified as hypolipidemic agents, although they may be used for purposes other than lowering cholesterol. They are used in the treatment of chronic diarrhea due to bile acid malabsorption.

<span class="mw-page-title-main">Malabsorption</span> Medical condition

Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety of anaemias.

<span class="mw-page-title-main">Small intestinal bacterial overgrowth</span> Medical condition

Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon, which is rich with bacteria, the small bowel usually has fewer than 100,000 organisms per millilitre. Patients with bacterial overgrowth typically develop symptoms which may include nausea, bloating, vomiting, diarrhea, malnutrition, weight loss and malabsorption, which is caused by a number of mechanisms.

<span class="mw-page-title-main">Short bowel syndrome</span> Medical condition

Short bowel syndrome is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may include bloating, heartburn, feeling tired, lactose intolerance, and foul-smelling stool. Complications can include anemia and kidney stones.

<span class="mw-page-title-main">Colestyramine</span> Pharmaceutical drug

Colestyramine (INN) or cholestyramine (USAN) is a bile acid sequestrant, which binds bile in the gastrointestinal tract to prevent its reabsorption. It is a strong ion exchange resin, which means it can exchange its chloride anions with anionic bile acids in the gastrointestinal tract and bind them strongly in the resin matrix. The functional group of the anion exchange resin is a quaternary ammonium group attached to an inert styrene-divinylbenzene copolymer.

<span class="mw-page-title-main">Chenodeoxycholic acid</span> Chemical compound

Chenodeoxycholic acid is a bile acid. Salts of this carboxylic acid are called chenodeoxycholates. Chenodeoxycholic acid is one of the main bile acids. It was first isolated from the bile of the domestic goose, which gives it the "cheno" portion of its name.

<span class="mw-page-title-main">Bile acid</span> Steroid acid found predominantly in the bile of mammals and other vertebrates

Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.

<span class="mw-page-title-main">Blind loop syndrome</span> Medical condition

Blind loop syndrome, also known as stagnant loop syndrome, is a state that occurs when the normal bacterial flora of the small intestine proliferates to numbers that cause significant derangement to the normal physiological processes of digestion and absorption. In some cases of blind loop syndrome, overgrowth of pathogenic non-commensal bacteria has also been noted. It has long been understood that from birth, and throughout life, large amounts of bacteria reside symbiotically within animal gastrointestinal tracts such as the human gastrointestinal tract. The understanding of this gut flora has even led to novel treatments for bowel irregularity that utilize so called "probiotics" or good bacteria that aid in normal digestion. The problem of blind loop syndrome arises when the bacterial colonies residing in the upper gastrointestinal tract begin to grow out of control or are altered in their makeup thereby creating a burden on the normal physiological processes occurring in the small intestine. This results in problems, among others, of: vitamin B12 deficiency, fat malabsorption and steatorrhea, fat-soluble vitamin deficiencies and intestinal wall injury.

Postcholecystectomy syndrome (PCS) describes the presence of abdominal symptoms after a cholecystectomy.

Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer. Many affected people are cancer survivors who had treatment for cervical cancer or prostate cancer; it has also been termed pelvic radiation disease with radiation proctitis being one of the principal features.

<span class="mw-page-title-main">Colesevelam</span> Pharmaceutical drug

Colesevelam is a bile acid sequestrant administered orally. It was developed by GelTex Pharmaceuticals and later acquired by Genzyme. It is marketed in the U.S. by Daiichi Sankyo under the brand name Welchol and elsewhere by Genzyme as Cholestagel. In Canada, it is marketed by Valeant as Lodalis.

<span class="mw-page-title-main">Colestipol</span> Chemical compound

Colestipol is a bile acid sequestrant used to lower blood cholesterol, specifically low-density lipoprotein (LDL). It is also used to reduce stool volume and frequency, and in the treatment of chronic diarrhea.

Jejunoileal bypass (JIB) was a surgical weight-loss procedure performed for the relief of morbid obesity from the 1950s through the 1970s in which all but 30 cm (12 in) to 45 cm (18 in) of the small bowel were detached and set to the side.

<span class="mw-page-title-main">Ileal sodium/bile acid cotransporter</span> Protein-coding gene in the species Homo sapiens

Ileal sodium/bile acid cotransporter, also known as apical sodium–bile acid transporter (ASBT) and ileal bile acid transporter (IBAT), is a bile acid:sodium symporter protein that in humans is encoded by the SLC10A2 gene.

<span class="mw-page-title-main">Colestilan</span> Chemical compound

Colestilan is a medication that acts as a phosphate binder and bile acid sequestrant. It is an ion-exchange resin, is an orally administered bile acid sequestrant that is being developed by Mitsubishi Tanabe Pharma Corporation for the treatment of hypercholesterolaemia and hyperphosphataemia. It has been launched in Japan for hypercholesterolaemia. For the treatment of hyperphosphataemia, it is launched in Austria, Germany, the Czech Republic, Portugal and the United Kingdom, is registered in the EU. Phase III development in paediatric patients with hyperphosphataemia associated with chronic kidney disease was underway in the UK and Germany. However, the company discontinued the development. In addition, the phase II development in type-2 diabetes mellitus and phase I development in hyperphosphataemia, in Japan, was also discontinued by the company.

Chronic diarrheaof infancy, also called toddler's diarrhea, is a common condition typically affecting up to 1.7 billion children between ages 6–30 months worldwide every year, usually resolving by age 4. According to the World Health Organization (WHO), diarrheal disease is the second greatest cause of death in children 5 years and younger. Diarrheal disease takes the lives of 525,000 or more children per year. Diarrhea is characterized as the condition of passing of three or more loose or watery bowel movements within a day sometimes with undigested food visible. Diarrhea is separated into three clinical categories; acute diarrhea may last multiple hours or days, acute bloody diarrhea, also known as dysentery, and finally, chronic or persistent diarrhea which lasts 2–4 weeks or more. There is normal growth with no evidence of malnutrition in the child experiencing persistent diarrhea. In chronic diarrhea there is no evidence of blood in the stool and there is no sign of infection. The condition may be related to irritable bowel syndrome. There are various tests that can be performed to rule out other causes of diarrhea that don't fall under the chronic criteria, including blood test, colonoscopy, and even genetic testing. Most acute or severe cases of diarrhea have treatment guidelines revolving around prescription or non prescription medications based on the cause, but the treatment protocols for chronic diarrhea focus on replenishing the body with lost fluids and electrolytes, because there typically isn't a treatable cause.

Bile acid malabsorption (BAM), known also as bile acid diarrhea, is a cause of several gut-related problems, the main one being chronic diarrhea. It has also been called bile acid-induced diarrhea, cholerheic or choleretic enteropathy, bile salt diarrhea or bile salt malabsorption. It can result from malabsorption secondary to gastrointestinal disease, or be a primary disorder, associated with excessive bile acid production. Treatment with bile acid sequestrants is often effective. It is recognised as a disability in the United Kingdom under the Equality Act 2010

<span class="mw-page-title-main">7α-Hydroxy-4-cholesten-3-one</span> Chemical compound

7α-Hydroxy-4-cholesten-3-one is an intermediate in the biochemical synthesis of bile acids from cholesterol. Its precursor, 7α-hydroxycholesterol, is produced from cholesterol by hepatic cholesterol 7α-hydroxylase (CYP7A1).

References

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  9. Nyhlin, H; Merrick, MV; Eastwood, MA (1994). "Bile acid malabsorption in Crohn's disease and indications for its assessment using SeHCAT". Gut. 35 (1): 90–3. doi:10.1136/gut.35.1.90. PMC   1374639 . PMID   8307458.
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  11. Walters, JR (2010). "Defining primary bile acid diarrhea: making the diagnosis and recognizing the disorder". Expert Review of Gastroenterology & Hepatology . 4 (5): 561–7. doi:10.1586/egh.10.54. PMID   20932141. S2CID   27123642.
  12. Wedlake, L; A'Hern, R; Russell, D; Thomas, K; Walters, JR; Andreyev, HJ (2009). "Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome". Alimentary Pharmacology & Therapeutics. 30 (7): 707–17. doi: 10.1111/j.1365-2036.2009.04081.x . PMID   19570102.