Dehydrocholic acid

Absorption

The duodenal experiment indicates that dehydrocholic acid is absorbed from the proximal small intestine .

Toxicity

Oral LD50, intravenous LD50, and intramuscular LD50 in rat is 4000 mg/kg, 750 mg/kg, and 1500 mg/kg, respectively . Oral LD50, subcutaneous LD50, and intravenous LD50 in mouse is 3100 mg/kg, 1620 mg/kg, and 1492 mg/kg, respectively . There have been no reports of overdose with dehydrocholic acid.

Chemical properties

white to off-white amorphous powder

Originator

Dehydrocholic Acid,New Zealand Pharmaceuticals Limited (NZP)

The Uses of Dehydrocholic acid

Dehydrocholic Acid is a derivative of Cholic Acid (C432600). a choleretic produced by, and isolated from liver cells.

The Uses of Dehydrocholic acid

antibacterial

Background

Dehydrocholic acid is a synthetic bile acid that was prepared from the oxidation of cholic acid with chromic acid . It has been used for stimulation of biliary lipid secretion. The use of dehydrocholic acid in over-the-counter products has been discontinued by Health Canada.

What are the applications of Application

Dehydrocholic acid is used in the production of chenodeoxycholic acid by bioconversion

Indications

No approved therapeutic indications.

Definition

ChEBI: 3,7,12-trioxo-5beta-cholanic acid is an oxo-5beta-cholanic acid in which three oxo substituents are located at positions 3, 7 and 12 on the cholanic acid skeleton. It has a role as a gastrointestinal drug. It is an oxo-5beta-cholanic acid, a 7-oxo steroid, a 12-oxo steroid and a 3-oxo-5beta-steroid. It is a conjugate acid of a 3,7,12-trioxo-5beta-cholan-24-oate.

Manufacturing Process

A.) Oxidation of cholic acid:
A solution, consisting of 15.40 g of cholic acid and 18.75 g of anhydrous sodium acetate in a solvent mixture of 20 ml of ethyl acetate, 30 ml of glacial acetic acid, and 30 ml of water, was prepared. This solution was cooled to 20°C. Chlorine gas was bubbled into the solution with vigorous stirring while the reaction temperature was maintained at 20°C. The chlorine was delivered at a constant rate of about 2.5 g per hour over a 4-hour period. The total amount of chlorine gas was 9.80 g which corresponds to about 3.68 moles per mole of cholic acid, or approximately a 23% excess. The solution temperature was maintained in the range of 16° to 20°C during the entire addition of chlorine. Initially the cholic acid solution was very dark-colored. As the reaction progressed, the solution became pale yellow and a precipitate of sodium chloride deposited. A considerable amount of product and sodium chloride precipitated during the latter stages of the reaction so that the final reaction mixture was a heavy slurry which was difficult to stir. After the addition of chlorine was complete, the slurry was aged one hour with stirring at 20°C. The excess chlorine was then discharged by dropwise addition of 10% aqueous sodium sulfite until the solution gave a negative test to starchiodide paper. The semi-crystalline slurry was then diluted with water to raise the total volume to 225 ml. The water was added dropwise with stirring over a 1-hour period. The ethyl acetate was then distilled off at 65-88°C. The resulting crystalline slurry was cooled to below 70°C and filtered through a sintered-glass funnel of medium porosity. The filter cake was washed until the filtrate gave a negative halide test with silver nitrate solution and then was sucked partially dry on the funnel. Drying was completed in a drier at 110°C for 3 hours. The product was crude pale tan dehydrocholic acid. Yield 14.3 (95%); M.P. 225-231°C.
B.) Purification of dehydrocholic acid:
To a chromatographic column, packed with 6.67 g of charcoal ("Nuchar C") with layers of sea sand at either end, 75 ml of acetone was added to wet the carbon. The column was heated to 40°C, and 25 ml of acetone was drained off. A solution of 20 g of dry crude dehydrocholic acid in 500 ml of acetone was poured into a reservoir atop the column and maintained in this reservoir at 40°C. This solution was then allowed to drop through the column at a constant rate over a 3-hour period. The column was then washed with 250 ml of acetone flowing through the column at a constant rate over a 1-hour-period at 40°C. The column effluent and wash acetone were combined and concentrated to a residual volume of about 100 ml which resulted in the formation of a thick slurry. The slurry was cooled with stirring at 0° to 5°C and aged for 30 min at this temperature. The slurry was filtered and the filter cake washed with cold acetone. The filter cake of U.S.P. dehydrocholic acid was sucked partially dry on the filter and then dried at 110°C for 3 hours. Yield 15 g to 17 g (75% to 85%).
A second crop of crystals was obtained from the combined filtrate and wash liquid from the first crop filtration. This mixture, which initially had a volume of about 100 ml, was concentrated to 20 ml. 10 ml of water was added to the solution and 10 ml of acetone mixed with a small amount of water distilled off. The residual thick slurry of dehydrocholic acid was cooled to 0-5°C, aged at this temperature with stirring for 30 min, and filtered. The filter cake was washed with acetone at 0°C, partially dried by suction on the filter, and then dried for three hours at 110°C. Yield 1 to 2 g (5% to 10%).

brand name

Decholin Sodium (Bayer).

Therapeutic Function

Choleretic, Diuretic, Diagnostic aid

Biochem/physiol Actions

Dehydrocholic acid is an oxidation product of cholic acid by chromic acid that is not present in physiological conditions. When used in animal experiments, it stimulates bile secretion.

Pharmacokinetics

Following infusion of dehydrocholic acid (DHCA) in rats, the secretions of all the endogenous biliary bile acids were decreased within 30-60 minutes of infusion . Phospholipid secretion as well as cholesterol levels were also declined. The bile flow was increased after administration of dehydrocholic acid .

Metabolism

The major site of metabolism is proposed to be the liver. The major metabolite accounting for 70% of total detectable metabolites is dihydroxymonoketo bile acid (3α,7α-dihydroxy-12-keto-5β-cholanoic acid). About 20% of metabolites is monohydroxydiketoacid (3α-hydroxy-7,12-keto-5β-cholanoic acid) and about 10% is cholic acid .