Chenodeoxycholic Acid

4.15

4.15

89.9

0.0899 mg/mL

168-171

165 - 167 °C

203.3 Ų [M-H]- [CCS Type: DT; Buffer gas: N2; Ionization: ESI-; Dataset: Bile Acids]

202.8 Ų [M+H-H2O]+ [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]；205.8 Ų [M+Na-H+HCOO]- [CCS Type: DT; Method: single field calibrated]；199.2 Ų [M+Na-H+Cl]- [CCS Type: DT; Method: single field calibrated]；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]；201.9 Ų [M+HCOO]- [CCS Type: DT; Method: single field calibrated]

192.83 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；198.15 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]；195.52 Ų [M+Na]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

206.57 Ų [M-H]- [CCS Type: DT; Method: stepped-field]

201.51 Ų [M-H]- [CCS Type: DT; Method: single field calibrated with Agilent tune mix (Agilent)]

205.9 Ų [M-H]-

This chemical does not meet GHS hazard criteria for 8.3% (1 of 12) of reports.

Warning

H302 (16.7%): Harmful if swallowed [Warning Acute toxicity, oral]；H312 (16.7%): Harmful in contact with skin [Warning Acute toxicity, dermal]；H315 (41.7%): Causes skin irritation [Warning Skin corrosion/irritation]；H319 (41.7%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]；H332 (16.7%): Harmful if inhaled [Warning Acute toxicity, inhalation]；H335 (16.7%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]；H361 (33.3%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 12 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.；Reported as not meeting GHS hazard criteria per 1 of 12 reports by companies.；There are 7 notifications provided by 11 of 12 reports by companies with hazard statement code(s).；Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website.

Hazard Traits - Developmental Toxicity；Authoritative List - Prop 65；Report - regardless of intended function of ingredient in the product

Status: Active Update: 19-04-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/5782

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.；Likelihood score: E* (Suspected but unproven cause of clinically apparent liver injury).

Drug Induced Liver Injury Rank (DILIrank 2.0)

Chenodiol

Ambiguous-DILI-concern

8

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

◉ Summary of Use during Lactation；Chenodiol (chenodeoxycholic acid) and its conjugates are naturally present in human milk, with higher milk levels of chenodiol conjugates in obesity. Chenodiol has not been measured in milk after administration as a drug. Chenodiol in the infant’s gastrointestinal tract enhances intestinal motility. No special precautions are required if mothers are taking chenodiol, but observe the infant for diarrhea.；◉ Effects in Breastfed Infants；Chenodiol acts directly on enterochromaffin cells in the gastrointestinal tract to stimulate 5-hydroxytryptamine secretion, which regulates gastrointestinal motility. Chenodiol stool levels were higher in breastfed infants with increased defecation frequency than in infants with normal or lower frequency.；◉ Effects on Lactation and Breastmilk；Relevant published information was not found as of the revision date.

Hazard Traits - Developmental Toxicity；Authoritative List - Prop 65；Report - regardless of intended function of ingredient in the product

Status: Active Update: 19-04-2018 https://echa.europa.eu/registration-dossier/-/registered-dossier/5782

A - Alimentary tract and metabolism；A05 - Bile and liver therapy；A05A - Bile therapy；A05AA - Bile acids and derivatives；A05AA01 - Chenodeoxycholic acid

QA - Alimentary tract and metabolism；QA05 - Bile and liver therapy；QA05A - Bile therapy；QA05AA - Bile acids and derivatives；QA05AA01 - Chenodeoxycholic acid

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.

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.

0GEI24LG0J

CHENODIOL

Established Pharmacologic Class [EPC] - Bile Acid

Chemical Structure [CS] - Bile Acids and Salts

Chenodiol is a Bile Acid.

CHENODIOL

Agents that are used to stimulate evacuation of the bowels.

Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion.

Chenodiol is well absorbed from the small intestine.

About 80% of its bacterial metabolite lithocholate is excreted in the feces.