Chenodeoxycholic acid (CDCA), also known as chenodiol, is a naturally occurring primary bile acid synthesized in the liver and present in high concentrations in bile. Therapeutically, it is used to dissolve cholesterol gallstones in patients who are not candidates for surgery. Chronic CDCA therapy has been associated with transient elevations in serum aminotransferase levels in up to 30% of patients. These elevations typically occur within two months of initiating treatment and are generally mild and reversible, often returning to normal ranges without the need to discontinue therapy. Liver biopsies performed during treatment usually reveal mild, nonspecific changes. Clinically apparent liver injury with jaundice is rare, with only a few cases reported in the literature. The liver enzyme elevations are often dose-related and may not recur upon reintroduction of the drug at lower doses.
BRAND NAMES
Chenix: An earlier brand name for chenodiol, approved in 1983 for the treatment of gallstones.
Chenodal: Approved in 2009 for gallstone dissolution; it was later granted orphan drug designation for the treatment of cerebrotendinous xanthomatosis (CTX).
Ctexli: The most recent brand name, approved by the U.S. FDA in February 2025 specifically for the treatment of CTX.
Generic Chenodiol: Chenodeoxycholic acid is also available in its generic form under the name chenodiol.
MECHANISM OF ACTION
Chenodeoxycholic acid (chenodiol) functions by inhibiting hepatic synthesis of both cholesterol and cholic acid. This suppression leads to a gradual replacement of cholic acid and its metabolite, deoxycholic acid, within the bile acid pool. Consequently, the bile becomes less saturated with cholesterol, facilitating the dissolution of radiolucent cholesterol gallstones in patients with a functioning gallbladder, as visualized by oral cholecystography. Additionally, chenodiol acts as a ligand for the farnesoid X receptor (FXR), a nuclear receptor that regulates the synthesis and transport of bile acids, thereby contributing to the maintenance of bile acid homeostasis.
PHARMACOKINETICS:
Absorption
Chenodeoxycholic acid (CDCA) is efficiently absorbed from the small intestine and re-circulated to the liver via a process known as enterohepatic circulation. The absorption process is highly effective, allowing the body to recycle most of its bile acid pool multiple times per meal.
Distribution
Chenodeoxycholic acid (CDCA) is a primary bile acid synthesized in the liver and distributed throughout the enterohepatic circulation to aid in digestion. In addition to its primary digestive role, CDCA is found in other tissues and organs where it acts as a signaling molecule.
Metabolism
Chenodiol is absorbed in the small intestine, converted in the liver to taurine and glycine conjugates, and excreted in bile. At steady state, some reaches the colon and is transformed by bacteria into lithocholic acid, about 80% of which is excreted in feces. The rest is reabsorbed and converted to poorly absorbed sulfolithocholyl conjugates. During therapy, biliary lithocholate rises slightly, while fecal bile acids increase three- to fourfold.
Excretion
Chenodeoxycholic acid (CDCA) is mainly eliminated through bile, being secreted by the liver after conjugation with taurine and glycine.
PHARMACODYNAMICS
It works by lowering cholesterol levels in bile, promoting the dissolution of gallstones composed mainly of cholesterol. Chenodeoxycholic acid is not effective for stones with high calcium or bile acid content.
ADMINISTRATION
Chenodeoxycholic acid (chenodiol) is taken orally in capsule or tablet form under medical supervision. It is prescribed for specific conditions such as cerebrotendinous xanthomatosis (CTX) and certain cholesterol-based gallstones.
DOSAGE AND STRENGTH
Chenodeoxycholic acid is available in oral tablet or capsule form, typically at a strength of 250 mg per dose. The dosage is adjusted based on the specific condition being treated and the patient’s individual response.
For the dissolution of cholesterol gallstones, the usual adult dose ranges from 13 to 16 mg/kg per day, divided into two doses and taken with meals. Treatment may continue for up to two years, depending on the size and composition of the gallstones.
In patients with cerebrotendinous xanthomatosis (CTX), the usual adult dose is 250 mg to 750 mg daily, divided into two or three doses.
DRUG INTERACTIONS
Chenodeoxycholic acid, also known as chenodiol, has several significant drug interactions that can impact its effectiveness or increase the risk of adverse effects. Patients should always inform their doctor about all medications and supplements they are taking to avoid potential problems.
FOOD INTERACTIONS
While there are no direct interactions between chenodeoxycholic acid and most foods, dietary factors can significantly influence its effectiveness, particularly when the medication is used to dissolve gallstones. The absorption and function of this bile acid are tied to food intake and overall diet.
CONTRAINDICATIONS
Chenodeoxycholic acid is contraindicated in individuals with specific pre-existing medical conditions, particularly those involving the liver, bile ducts, or intestines. It should not be used in patients with active liver disease, biliary obstruction, cholecystitis (inflammation of the gallbladder), or biliary fistula, as these conditions can interfere with the drug’s metabolism and excretion.
SIDE EFFECTS
Diarrhea (most common; affects about 30–40% of patients)
Abdominal cramps or pain
Nausea and vomiting
Constipation
Heartburn or indigestion
Bloating or excessive gas
Loss of appetite
OVER DOSE
Primary symptom: The most common sign of overdose is severe diarrhea, due to excessive bile acid levels in the intestine.
Other possible effects: Nausea, vomiting, abdominal pain, and electrolyte imbalance (from fluid loss) may also occur.
Liver-related effects: Prolonged or significant overdose can cause elevated liver enzyme levels or hepatic dysfunction.
Management: There is no specific antidote for chenodeoxycholic acid overdose. Treatment is symptomatic and supportive, focusing on restoring fluid and electrolyte balance.
Medical attention: Patients showing signs of overdose should stop the medication immediately and seek medical assistance for monitoring and supportive care.
TOXICITY
Chenodeoxycholic acid (CDCA) exhibits a toxicity profile that varies between humans and other primates, mainly because of differences in the metabolism of its toxic by product, lithocholic acid. In humans, it may cause temporary elevations in liver enzyme levels, while serious liver damage is uncommon.
