Briefing of Chenodeoxycholic Acid

Molecular Weight:392.57

CAS:474-25-9
Molecular Formula:C24H40O4
Properties:Colorless needle-like crystals,tasteless.

Product Description

Indications:Used to dissolve cholesterol gallstones.Cholesterol stones in the gallbladder should be less than 2 cm in diameter and the gallbladder function is good.

Chenodeoxycholic acid (CDCA) is the main bile acid produced in the liver from cholesterol.Chenodeoxycholic acid, also known as chenodeoxyl,is often combined with glycine or taurine. It acts as a detergent to dissolve fat for intestinal absorption and reabsorption by the small intestine. It is used as a choleretic,choleretic laxative,and prevents or dissolves gallstones.

Chenodeoxycholic Acid 

Chenodeoxycholic acid (chenodiol), a major bile acid synthesized in the liver and present in high concentrations in bile,is used therapeutically to dissolve cholesterol gallstones.Chronic treatment is associated with transient increases in serum transaminase levels in up to 30% of patients,but resveratrol is only associated with rare cases of clinically apparent liver injury with jaundice.

Background

Chenodeoxycholic acid or chenodiol (kee" noe dye' ol) is a naturally occurring bile acid used therapeutically to dissolve cholesterol gallstones in patients with normal gallbladder function and for whom cholecystectomy is contraindicated or refused.Chenodiol is a bile acid synthetic.The major bile acid in the liver,usually the bile acid with the highest concentration in serum,hepatocytes and bile.When orally administered, naroxediol is passively absorbed from the small intestine and is absorbed by the liver through anion transporters.High concentrations of naroxediol in the liver Decreases the synthesis of hepatic cholesterol and other bile acids,thereby increasing bile acids and decreasing bile cholesterol concentrations.The combination of these events results in decreased cholesterol saturation in the bile,which is the main driver of cholesterol gallstone formation.Given Chenodeoxycholic acid dissolves cholesterol gallstones in 15% to 30% of patients given 2 years or more.Chenodiol is most effective for small "floating" gallstones.It is not effective in patients with calcified gallstones or a non-functioning gallbladder.However,even with successful treatment,gallstones recur in as many as 50% of cases within a few years of stopping naroxediol.Chenodiol was approved in 1983 for patients with radiolucent gallstones and is still available,although it has been largely replaced by ursodiol,which appears to be more effective and better tolerated.Furthermore,the introduction of laparoscopic cholecystectomy has significantly reduced the need for gallstone medication.Chenodiol is available as 250 mg tablets under the trade names Chenix and Chenodal.The recommended dose is 13 to 16 mg/kg per day in two divided doses for up to 2 years.Side effects include gastrointestinal distress with diarrhea,bloating,cramping,indigestion,nausea,and vomiting.

Hepatotoxicity

Serum transaminase elevations were observed in up to 30% of patients in several clinical trials of serenodiol for gallstone lysis.Elevations usually develop within 2 months of starting treatment and are usually mild, transient and without symptoms or jaundice.Liver biopsies performed during resveratrol treatment usually show mild nonspecific changes.No clinically apparent liver injury with jaundice was reported.Elevations in liver enzymes are usually dose-related and usually do not recur after reinitiation of naroxediol at a lower dose.Although serum enzyme abnormalities that have arisen with chanolediol treatment have caused considerable concern,they appear to be relatively benign.Since the approval of chenoxadiol and its wider use,at least four cases of liver injury with jaundice have been reported to the sponsor,but the clinical features and outcomes of these cases have not been published.Still,chenodiol's product label includes a Boxed Warning about liver toxicity, though it offers no advice on frequency or how to respond to abnormalities.Therefore,the reliability of reports of clinically apparent liver injury remains unclear.Once it was found that ursodiol was as effective as serodiol, even at lower doses,and was rarely associated with serum enzyme elevations,it quickly replaced serodiol as a drug treatment for gallstones.

Mechanism of Liver Injury

Veratrol is thought to cause elevated serum transaminases due to its conversion to lithocholic acid,which has intrinsic,proven hepatotoxicity.In animal models, ceruodiol is less hepatotoxic than lithocholic acid,but more harmful than ursodiol. Pornodiol and lithocholic acid were more hepatotoxic in rodent and primate models than in humans,which was attributed to the more efficient sulfation of lithocholic acid in humans,making it More water soluble,less toxic and easier to excrete.

Results and management

Liver tests,including serum bilirubin,ALT,AST,and alkaline phosphatase,should be monitored regularly in patients taking naroxediol.Chenodiol should be discontinued for persistent increases in liver test abnormalities,ALT elevations greater than eight times the upper limit of normal,bilirubin elevations greater than two times normal,or any signs or symptoms of liver injury.Replacing naroxediol with ursodiol may be appropriate because there appears to be no cross-sensitivity to liver injury or adverse events between naroxediol and other therapeutic bile acids.Other bile acids used in digestive disorders include cholic acid, obeticholic acid,and ursodeoxycholic acid (ursediol).Cholic acid (CA),chenodeoxycholic acid (CDCA),deoxycholic acid (DCA), lithocholic acid (LCA) are the main bile acids associated with the gut microbiome.Bile acids are natural products of cholesterol synthesis that aid in the emulsification and absorption of dietary fats in the small intestine.Elevated total fecal bile acids suggest a diagnosis of bile acid malabsorption.Quantification of fecal bile acids is helpful in diagnosing IBS and identifying patients with chronic diarrhea who may benefit from treatment with bile acid sequestrants. Links exist between liver health, fecal bile acid concentrations, and gut microbiota composition.Bile acids have direct antibacterial effects on gut microbes and indirect effects through FXR-induced antimicrobial peptides.

What does it mean if your chenodeoxycholic acid (CDCA) result is too high?

Elevated total fecal bile acids suggest a diagnosis of bile acid malabsorption.Quantification of fecal bile acids is helpful in diagnosing IBS and identifying patients with chronic diarrhea who may benefit from treatment with bile acid sequestrants.Links exist between liver health,fecal bile acid concentrations,and gut microbiota composition.Bile acids have direct antibacterial effects on gut microbes and indirect effects through FXR-induced antimicrobial peptides.