URSODIOL
Chemistry
A naturally occurring bile acid, ursodiol, also known as ursodeoxycholic acid has a molecular weight of 392.6.Storage, Stability, Compatibility
Unless otherwise specified by the manufacturer, ursodiol capsules should be stored at room temperature (15-30°C) in tight containers.Pharmacology - URSODIOL
After oral administration, ursodiol suppresses hepatic synthesis and secretion ofcholesterol. Ursodiol also decreases intestinal absorption of cholesterol. By reducing cholesterolsaturation in the bile it is thought that ursodiol allows solubilization of cholesterol-containinggallstones. Ursodiol also increases bile flow and in patients with chronic liver disease it apparentlyreduces the hepatocyte toxic effects of bile salts by decreasing their detergent action, and mayprotect hepatic cells from toxic bile acids (e.g., lithocholate, deoxycholate and chenodeoxycholate).Uses, Indications - In small animals, ursodiol may be useful as adjunctive therapy for the medicalmanagement of cholesterol-containing gallstones and/or in patients with chronic liver disease, particularly where cholestasis (bile toxicity) plays an important role.
Pharmacokinetics - URSODIOL
Ursodiol is well absorbed from the small intestine after oral administration. Inhumans, up to 90% of dose is absorbed. After absorption, it enters the portal circulation. In the liverit is extracted and combined (conjugated) with either taurine or glycine and secreted into the bile.Only very small quantities enter the systemic circulation and very little is detected in the urine. Aftereach entero-hepatic cycle, some quantities of conjugated and free drug undergoes bacterialdegradation and eventually most of the drug is eliminated in the feces after being oxidized orreduced to less soluble compounds. Ursodiol detected in the systemic circulation is highly bound toplasma proteins.
Contraindications, Precautions, Reproductive Safety
Patients sensitive to other bile acidproducts may also be sensitive to ursodiol. The benefits of using ursodiol should be weighedagainst its risks in patients with complications associated with gallstones (e.g., biliary obstruction, biliary fistulas, cholecystitis, pancreatitis, cholangitis). While ursodiol may be useful in treatingpatients with chronic liver disease, some patients may experience further impairment of bile acidmetabolism.Ursodiol's safety during pregnancy has not been unequivocally established, but studies in rats atdoses up to 100 times those given therapeutically in humans demonstrated no adversity to fetuses.
It is unknown whether the drug enters breast milk, but no problems have thus far been reported andit would unlikely be of concern (due to the very low systemic levels of the drug present).
Adverse Effects, Warnings
While hepatotoxicity has not been associated with ursodiol therapy, some human patients have an inability to sulfate lithocholic acid (a naturally occurring bile acid andalso a metabolite of ursodiol). Lithocholic acid is a known hepatotoxin; veterinary significance isunclear. Diarrhea and other GI effects have rarely been noted in humans taking ursodiol. Ursodiolwill not dissolve calcified, radiopaque stones or radiolucent bile pigment stones.Overdosage, Acute Toxicity - Overdosage of ursodiol would most likely cause diarrhea.
Treatment, if required, could include supportive therapy; oral administration of an aluminum-containing antacid (e.g., aluminum hydroxide suspension); gastric emptying (if large overdose) withconcurrent administration of activated charcoal or cholestyramine suspension.