Cholic Acid

Aluminum-based antacids have been shown to adsorb bile acids in vitro and can reduce the bioavailability of Cholbam. Take Cholbam at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after an aluminum-based antacid.

Bile acid binding resins such as cholestyramine, colestipol, or colesevelam adsorb and reduce bile acid absorption and may reduce the efficacy of Cholbam. Take Cholbam at least 1 hour before or 4 to 6 hours (or at as great an interval as possible) after a bile acid binding resin.

Phenobarbital treatment increases the transport capacity (Vmax) for bile salt in the ileum of the rat. ... Rats treated with phenobarbital for 10 days had a 4-fold smaller cholic acid pool compared to control rats. Additionally, the daily production of cholic acid was decreased in phenobarbital treated rats compared to control rats. Phenobarbital has an antagonistic effect to the desired action of cholic acid in patients and may potentially endanger the established metabolic control. Therefore use of Phenobarbital in patients treated with cholic acid has been contraindicated.

Avoid concomitant use of inhibitors of the bile salt efflux pump (BSEP) such as cyclosporine /with Cholbam/. Concomitant medications that inhibit canalicular membrane bile acid transporters such as the BSEP may exacerbate accumulation of conjugated bile salts in the liver and result in clinical symptoms. If concomitant use is deemed necessary, monitoring of serum transaminases and bilirubin is recommended.

For more Interactions (Complete) data for CHOLIC ACID (8 total), please visit the HSDB record page.

In small, open label trials, cholic acid was found to improve fat soluble vitamin absorption and to ameliorate many of the clinical features of the bile acid synthetic defects including improvement in serum aminotransferase levels, decrease in bilirubin and jaundice and improvement in general health and growth. In some instances, higher doses of cholic acid were associated with elevations in serum aminotransferase levels. These abnormalities, however, were mild, transient and rapidly reversed with lowering the daily dose. There have been no reports of clinically apparent liver injury with jaundice attributed to cholic acid therapy given in standard doses.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2600(SRC), determined from a structure estimation method(2), indicates that cholic acid is expected to have slight mobility in soil(SRC). However, the pKa of cholic acid is 4.98(3), indicating that this compound will exist largely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as an anion and anions do not volatilize. Cholic acid is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 9.7X10-15 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2015).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2600(SRC), determined from a structure estimation method(2), indicates that cholic acid is expected to adsorb to suspended solids and sediment(SRC). A pKa of 4.98(3) indicates cholic acid will exist largely in the anion form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process(SRC). According to a classification scheme(4), an estimated BCF of 3(SRC), from its log Kow of 2.02(5) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2015).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), cholic acid, which has an estimated vapor pressure of 5.2X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase cholic acid may be removed from the air by wet and dry deposition(SRC). Cholic acid does not contain chromophores that absorb at wavelengths >290 nm(4) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

IDENTIFICATION AND USE: Cholic acid is used in biochemical research, as a pharmaceutical intermediate, and as an emulsifying agent in foods (up to 0.1%). It is also a medication used for the treatment of bile acid synthesis disorders due to single enzyme defects and for the adjunctive treatment of peroxisomal disorders including Zellweger spectrum disorders in patients who exhibit manifestations of liver disease, steatorrhea or complications from decreased fat soluble vitamin absorption. HUMAN EXPOSURE AND TOXICITY: Cholic acid is a primary bile acid. Primary bile acids are biosynthesized in the liver and are key constituents of normal bile. When formulated and used as a treatment for patients with bile acid synthesis disorders the major toxic effect is on liver function. The dose of cholic acid to be administered to the patients is intended to restore a concentration that is equivalent to that physiologically present in humans. Therefore any perceived genotoxic risk from cholic acid and deoxycholic acid to the patients would be equivalent to that of a normal healthy adult that produces these bile acids intrinsically. Overall, cholic acid showed nonsignificant mutagenic activity in a battery of genotoxicity tests performed in vitro. ANIMAL STUDIES: Bile acids are known to regulate bile acid synthesis and transport by the farnesoid X receptor in the liver (FXR-SHP) and intestine (FXR-Fgf15). Mice lacking the farnesoid X receptor (FXR) involved in the maintenance of hepatic bile acid levels are highly sensitive to cholic acid-induced liver toxicity. Serum aspartate aminotransferase (AST) activity was elevated 15.7-fold after feeding a 0.25% cholic acid diet for five days, whereas only slight increases in serum AST (1.7- and 2.5-fold) were observed in wild-type mice fed 0.25 and 1% cholic acid diet, respectively. Primary bile acids were studied as possible colon tumor promoters or inhibitors in a rat model of chemically induced colon cancer. Cholic acid feeding increased the number of animals with tumors, the number of tumors per animal, and the number of tumors per tumor-bearing animal. Tumor enhancement was attributed to deoxycholic acid, the bacterial metabolite of cholic acid. Administration of cholic acid (1.0% of the diet) to male rats for 3 days resulted in increased numbers of DNA synthesizing epithelial cells per colonic crypt column as compared to those found in either control or 0.2% cholic acid-fed rats. The mutagenicity of bile acids was detected by a fluctuation test using Salmonella typhimurium TA100 and TA98 as tester strains. Cholic acid and deoxycholic acid were mutagenic in this test. The mutagenicity of the bile acids on a molar basis was roughly one-fourth that of methyl methanesulfonate, a moderately potent mutagen. 0.5% cholic acid ingested by pregnant hamsters, caused ductal/ductular proliferation and hepatobiliary inflammatory damage in a different degree of intensity in adult animals and mild intensity in the young; and also the number of the young was reduced in the litter. The ingestion of these bile acids by hamsters, during gestational period caused different degrees of toxicity on maternal and neonatal hepatobiliary systems. In rat developmental studies there was apparent pathological change of fetal rats brain in cholic acid-treated groups, the neuronal degeneration and the mitochondria swelling was mainly found in low cholic acid group, the neuronal necrosis and the mitochondria decrease was mainly found in high cholic acid group.

Using a structure estimation method based on molecular connectivity indices(1), the Koc of cholic acid can be estimated to be 2600(SRC). According to a classification scheme(2), this estimated Koc value suggests that cholic acid is expected to have slight mobility in soil. However, soil mobility may be slightly higher given a measured log Kow of 2.02(3). The pKa of cholic acid is 4.98(4), indicating that this compound will exist largely in the anion form in the environment and anions generally do not adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(5).

/HUMAN EXPOSURE STUDIES/ Qualitative and quantitative changes in intralumenal bile acid composition may alter cholesterol absorption and synthesis and low-density lipoprotein (LDL) receptor expression. The role of cholic acid (CA) in cholesterol absorption in humans remains unclear and, thus, was examined in the current study. In a crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day (CA) or no bile acid supplement (control) while being fed a controlled diet (American Heart Association (AHA) heart-healthy diet). A liquid meal of defined composition was given on day 14 of the diet, and lumenal samples were collected. Thereafter, cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods from days 16 to 20. With CA treatment, bile was enriched significantly with CA (P < 0.0004) to 60.2% +/- 2.4% (mean +/- SEM) compared with 43.3% +/- 2.4% for controls. CA plus diet treatment significantly increased (P = 0.013) cholesterol absorption (72.6% +/- 2.9%) compared with diet treatment alone (60.4% +/- 2.9%). Percentage micellar cholesterol was increased by CA plus diet treatment vs. diet alone after meal ingestion (P = 0.004). Plasma total and high-density lipoprotein (HDL) and LDL cholesterol was unchanged with CA treatment. Thus, enrichment in lumenal bile with CA results in an increase in cholesterol absorption, an effect potentially mediated by enhanced cholesterol solubilization in micelles.

/HUMAN EXPOSURE STUDIES/ Clinical data has shown there to be four successful pregnancies in patients who had been receiving Orphacol, all producing healthy babies.

/SIGNS AND SYMPTOMS/ Discontinue treatment with Cholbam at any time if there are persistent clinical or laboratory indicators of worsening liver function or cholestasis. Concurrent elevations of serum gamma glutamyltransferase (GGT) and serum alanine aminotransferase (ALT) may indicate Cholbam overdose. Continue to monitor laboratory parameters of liver function and consider restarting at a lower dose when the parameters return to baseline.

/BIOMONITORING/ Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas-liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P =.04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P <.05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Cholic acid

Ambiguous-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

An estimated BCF of 3 was calculated in fish for cholic acid(SRC), using a log Kow of 2.02(1) and a regression-derived equation(2). According to a classification scheme(2), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including cholic acid, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

Found conjugated with glycine or taurine in the bile of most vertebrates; Used as a gallbladder stimulant; [Merck Index] Used in biochemical research, as an intermediate for pharmaceuticals, and as a food emulsifying agent; [Hawley]

Biochemical research, pharmaceutical intermediate, emulsifying agent in foods (up to 0.1%)

AGENT IN BIOCHEMICAL RESEARCH; CHEM INT FOR PHARMACEUTICALS

EMULSIFYING AGENT FOR EGG WHITES

MEDICATION

This is an endogenously produced metabolite found in the human body. It is used in metabolic reactions, catabolic reactions or waste generation.

(1972) PROBABLY GREATER THAN 4.54X10+5 GRAMS

(1975) PROBABLY GREATER THAN 4.54X10+5 GRAMS

ALKALINE EXTRACTION OF BOVINE BILE, NEUTRALIZATION WITH ACID, FORMATION OF THE MAGNESIUM SALT, FILTRATION, SEPARATION OF DEOXYCHOLIC ACID, AND ACIDIFICATION OF THE FILTRATE

Extraction from beef bile.

Derivation: From glycocholic and taurocholic acids in bile; organic synthesis.

Oral: 50 mg and 250 mg hard capsules, Orphacol (Active substance: Cholic acid)

Cholbam is available in two capsule strengths. 50 mg capsule: Size number 2 Swedish orange capsule with cap imprinted with "50 mg" and body imprinted with "ASK001". The capsules contain a white to off-white powder. 250 mg capsule: Size number 0 white capsule with a cap imprinted with "250 mg" and body imprinted with "ASK002". The capsules contain a white to off-white powder.

Food Additives -> EMULSIFIER -> JECFA Functional Classes

Cosmetics -> Solvent

Cholan-24-oic acid, 3,7,12-trihydroxy-, (3.alpha.,5.beta.,7.alpha.,12.alpha.)-: ACTIVE

MAJOR HUMAN BILE ACIDS ARE CHOLIC & DEOXYCHOLIC ACIDS & CHENODEOXYCHOLIC ACID... CHOLIC ACID & CHENODEOXYCHOLIC ACID ARE PRESENT IN BILE IN ABOUT EQUAL PROPORTIONS (30%-40%)...LESS DEOXYCHOLIC ACID (10%-20%). ...FORMED FROM CHOLESTEROL IN LIVER.

BILE ACIDS, PRESENT AS SODIUM SALTS OF A MIXTURE OF ACIDS, ARE DIVIDED INTO 2 GROUPS: 1) GLYCOCHOLIC ACIDS /CONJUGATES OF CHOLIC ACID WITH GLYCINE/ & 2) TAUROCHOLIC ACIDS. /CONJUGATES OF CHOLIC ACID WITH TOURINE/

The most abundant bile acid