indication

The drug reduces cholesterol absorption and is used to dissolve (cholesterol) gallstones in patients who want an alternative to surgery.

pharmacology

Ursodiol (also known as ursodeoxycholic acid) is one of the secondary bile acids, which are metabolic byproducts of intestinal bacteria. Primary bile acids are produced by the liver and stored in the gall bladder. When secreted into the colon, primary bile acids can be metabolized into secondary bile acids by intestinal bacteria. Primary and secondary bile acids help the body digest fats. Ursodeoxycholic acid helps regulate cholesterol by reducing the rate at which the intestine absorbs cholesterol molecules while breaking up micelles containing cholesterol. Because of this property, ursodeoxycholic acid is used to treat gall stones non-surgically.

mechanism of action

Ursodeoxycholic acid reduces elevated liver enzyme levels by facilitating bile flow through the liver and protecting liver cells. The main mechanism if anticholelithic. Although the exact process of ursodiol's anticholelithic action is not completely understood, it is thought that the drug is concentrated in bile and decreases biliary cholesterol by suppressing hepatic synthesis and secretion of cholesterol and by inhibiting its intestinal absorption. The reduced cholesterol saturation permits the gradual solubilization of cholesterol from gallstones, resulting in their eventual dissolution.

toxicity

Neither accidental nor intentional overdosing with ursodeoxycholic acid has been reported. Doses of ursodeoxycholic acid in the range of 16-20 mg/kg/day have been tolerated for 6-37 months without symptoms by 7 patients. The LD50 for ursodeoxycholic acid in rats is over 5000 mg/kg given over 7-10 days and over 7500 mg/kg for mice. The most likely manifestation of severe overdose with ursodeoxycholic acid would probably be diarrhea, which should be treated symptomatically.

route of elimination

Only small quantities of ursodiol appear in the systemic circulation and very small amounts are excreted into urine. Eighty percent of lithocholic acid formed in the small bowel is excreted in the feces, but the 20% that is absorbed is sulfated at the 3-hydroxyl group in the liver to relatively insoluble lithocholyl conjugates which are excreted into bile and lost in feces.

drug interactions

Cholestyramine: The resin decreases the effect of ursodiol

Clofibrate: The fibric acid derivative decreases the effect of ursodiol

Clomifene: Estrogens decreases the effect of ursodiol

Colesevelam: Bile Acid Sequestrants may decrease the serum concentration of Ursodiol. Consider administration of ursodiol 5 hours or more after bile acid sequestrants to minimize ursodiol adsorption in the gastrointestinal tract. Monitor for decreased therapeutic effects of ursodiol in patients receiving bile acid sequestrants.

Colestipol: The resin decreases the effect of ursodiol

Conjugated Estrogens: Estrogens decreases the effect of ursodiol

Cyclosporine: Ursodiol increases the levels of cyclosporine

Diethylstilbestrol: Estrogens decreases the effect of ursodiol

Estradiol: Estrogens decreases the effect of ursodiol

Ethinyl Estradiol: Estrogens decreases the effect of ursodiol

Fenofibrate: The fibric acid derivative decreases the effect of ursodiol

Gemfibrozil: The fibric acid derivative decreases the effect of ursodiol