Chenodeoxycholic acid

392.57200

392.57

207-481-8

0GEI24LG0J

DTXSID2020260

A05AA01|A - Alimentary tract and metabolism

2918990090

77.76000

4.47790

white to off-white crystalline powder

1.128g/cm3

119 °C

547.1ºC at 760 mmHg

298.8ºC

1.558

Practically insoluble in water

Store in a cool, dry place. Store in a tightly closed container.

201.51 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|206.57 Ų [M-H]- [CCS Type: DT, Method: stepped-field]|202.3 Ų [M-H]- [CCS Type: DT, Method: single field calibrated]|186.9 Ų [M+H-2H2O]+ [CCS Type: DT, Method: single field calibrated]|202.8 Ų [M+H-H2O]+ [CCS Type: DT, Method: single field calibrated]|201.9 Ų [M+HCOO]- [CCS Type: DT, Method: single field calibrated]|208.5 Ų [M+K-H+HCOO]- [CCS Type: DT, Method: single field calibrated]|224.5 Ų [M+K-H+HCOO]- [CCS Type: DT, Method: single field calibrated]|199.2 Ų [M+Na-H+Cl]- [CCS Type: DT, Method: single field calibrated]|205.8 Ų [M+Na-H+HCOO]- [CCS Type: DT, Method: single field calibrated]|205.9 Ų [M-H]-

NONH for all modes of transport

2

R63

S36/37-S45

FZ1980000

Xn

P305 + P351 + P338

H315-H319

Hepatotoxic.

In multiple clinical trials of chenodiol therapy for dissolution of gallstones, serum aminotransferase elevations occurred in up to 30% of patients. The elevations generally arose within 2 months of starting therapy and were typically mild, transient and not accompanied by symptoms or jaundice. Liver biopsies done during chenodiol therapy generally showed mild, nonspecific changes. Clinically apparent liver injury with jaundice was not reported. The liver enzyme elevations were generally dose related and usually did not recur on restarting chenodiol at lower doses. While the serum enzyme abnormalities that occurred on chenodiol therapy generated considerable concern, they appeared to be relatively benign. Since the approval of chenodiol and its more widespread use, at least four instances of liver injury with jaundice have been reported to the sponsor, but the clinical features and outcomes of these cases have not been published. Nevertheless, the product label for chenodiol includes a boxed warning about hepatotoxicity although it does not provide advice on the frequency or how to respond to abnormalities. Thus, the reliability of reports of clinically apparent liver injury with chenodiol therapy remains unclear. Once ursodiol was found to be equally as effective as chenodiol, even at lower doses, and was rarely associated with serum enzyme elevations, it rapidly replaced chenodiol as medical therapy for gallstones.

Chenodiol is indicated for patients with radiolucent stones in well-opacifying gallbladders, in whom selective surgery would be undertaken except for the presence of increased surgical risk due to systemic disease or age. Chenodiol will not dissolve calcified (radiopaque) or radiolucent bile pigment stones.|FDA Label|Chenodeoxycholic acid is indicated for the treatment of inborn errors of primary bile acid synthesis due to sterol 27 hydroxylase deficiency (presenting as cerebrotendinous xanthomatosis (CTX)) in infants, children and adolescents aged 1 month to 18 years and adults.,

Chenodeoxycholic acid (chenodiol) is a primary bile acid, synthesized in the liver and present in high concentrations in bile that is used therapeutically to dissolve cholesterol gallstones. Chronic therapy is associated with transient elevations in serum aminotransferase levels in up to 30% of patients, but chenodiol has been linked to only rare instances of clinically apparent liver injury with jaundice.

Gastrointestinal Agents

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.

Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. (See all compounds classified as Gastrointestinal Agents.)|Agents that are used to stimulate evacuation of the bowels. (See all compounds classified as Cathartics.)

Chenodiol is well absorbed from the small intestine.|About 80% of its bacterial metabolite lithocholate is excreted in the feces.

Chenodiol is well absorbed from the small intestine and taken up by the liver where it is converted to its taurine and glycine conjugates and secreted in bile. At steady-state, an amount of chenodiol near the daily dose escapes to the colon and is converted by bacterial action to lithocholic acid. About 80% of the lithocholate is excreted in the feces; the remainder is absorbed and converted in the liver to its poorly absorbed sulfolithocholyl conjugates. During chenodiol therapy there is only a minor increase in biliary lithocholate, while fecal bile acids are increased three- to fourfold.

Chenodiol suppresses hepatic synthesis of both cholesterol and cholic acid, gradually replacing the latter and its metabolite, deoxycholic acid in an expanded bile acid pool. These actions contribute to biliary cholesterol desaturation and gradual dissolution of radiolucent cholesterol gallstones in the presence of a gall-bladder visualized by oral cholecystography. Bile acids may also bind the the bile acid receptor (FXR) which regulates the synthesis and transport of bile acids.

Acid, Chenic

Human drugs -> Orphan -> Chenodeoxycholic acid Leadiant (previously known as Chenodeoxycholic acid sigma-tau) -> EMA Drug Category|Bile and liver therapy -> Human pharmacotherapeutic group|Human drugs -> Rare disease (orphan)|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Lipids -> Sterol Lipids [ST] -> Bile acids and derivatives [ST04] -> C24 bile acids, alcohols, and derivatives [ST0401]