Chenodeoxycholic Acid

Chenodeoxycholic Acid (or Chenodiol) is an epimer of ursodeoxycholic acid (DB01586). Chenodeoxycholic Acid is a bile acid naturally found in the body. It works by dissolving the cholesterol that makes gallstones and inhibiting production of cholesterol in the liver and absorption in the intestines, which helps to decrease the formation of gallstones. It can also reduce the amount of other bile acids that can be harmful to liver cells when levels are elevated.

Chenodeoxycholic Acid is a bile acid that is used to treat gallstones. This is a chemical which occurs naturally in bile, where it helps control the concentration of cholesterol in the blood. As an orally administered drug it is given as an alternative to surgery in the treatment of gallstones. It acts by reducing levels of cholesterol in the bile, helping gallstones that are made predominantly of cholesterol to dissolve. Chenodeoxycholic Acid is ineffective with stones of a high calcium or bile acid content. Its benefits are increased by weight loss and a diet high in fibre and low in fat. The drug dissolves gallstones in 3 to 18 months and the progress of the treatment is assessed regularly by ultrasound or X-ray. To prevent recurrence of gallstones drug treatment my be continued after the stones have disappeared.

Other names for Chenodeoxycholic Acid include: Chenodiol, Chenic Acid, and CDCA.

The most abundant bile acids in humans are cholic acid and Chenodeoxycholic Acid. They are usually conjugated in amide linkage with the amino acid glycine or taurine. The cholic acid conjugates with glycine and taurine are called glycocholate and taurocholate, respectively.

Oral

Dissolution of cholesterol-rich gallstones

Adult: Initial: 250 mg bid for 2 wk; then titrate dose by 250 mg daily every wk until the recommended or max tolerated dosage is reached. Recommended

Maintenance: 13-16 mg/kg daily in 2 divided doses. Daily dose may be divided unequally with larger dose given before bedtime. Doses <10 mg/kg daily is not recommended (usually ineffective and may increase risk of cholecystectomy).

Hepatocyte dysfunction or bile ductal abnormalities (e.g. intrahepatic cholestasis, primary biliary cirrhosis or sclerosing cholangitits); patient with a gallbladder confirmed as nonvisualising after two consecutive single doses of dye; radiopaque stones; gallstone complications or compelling reasons for gallbladder surgery (e.g. unremitting acute cholecystitis, cholangitis, biliary obstruction, gallstone pancreatitis and biliary GI fistula); pregnancy.

Concurrent use of bile acid sequestrants (e.g. cholestyramine, colestipol); or aluminum-containing antacids may decrease absorption of Chenodeoxycholic Acid. Administration time should be separated apart if concurrent use of these products is necessary. Pharmacodynamics of coumarin derivatives may be affected due to hepatotoxic effect of Chenodeoxycholic Acid, resulting in prolongation of prothrombin time (PT) and increase risk of bleeding; monitor PT/INR. Estrogen, oral contraceptives, and clofibrate may increase biliary cholesterol secretion and thus reducing Chenodeoxycholic Acid efficacy.

Dose-related diarrhoea, nausea, vomiting, biliary pain, abdominal cramps, abdominal pain, epigastric distress, constipation, dyspepsia, flatulence, heartburn, anorexia, leukopenia, dose-related serum aminotransferase (mainly SGPT) elevations, increased LDL cholesterol, and increased total cholesterol.