Ursodiol, also known as ursodeoxycholic acid or UDCA, is a hydrophilic secondary bile acid derived from cholesterol with the empirical formula C24H40O4 and a molecular weight of approximately 392.6 g mol. Ursodiol is used to dissolve gallstones in people who do not want surgery or cannot have surgery to remove gallstones. Ursodiol is also used to prevent the formation of gallstones in overweight people who are losing weight very quickly. Technically, UDCA alters the composition and physical chemistry of bile by reducing hepatic secretion and intestinal absorption of cholesterol and by displacing more hydrophobic, potentially cytotoxic bile acids from the enterohepatic circulation. It is administered orally, undergoes conjugation with glycine or taurine in the liver, and participates in extensive enterohepatic recirculation; peak plasma concentrations are typically reached within one to a few hours after a dose and steady state is achieved over days to weeks. Clinical dosing is weight based with common adult regimens in the 8 to 10 mg per kg per day range divided across two or three doses for gallstone dissolution and certain cholestatic liver disorders. Key pharmacologic effects include reduction of bile cholesterol saturation, enhancement of bile flow, and hepatocellular membrane stabilization with documented antiapoptotic and cytoprotective properties. Common limitations include slow onset of action, need for prolonged treatment to achieve stone dissolution, lack of efficacy for calcified or pigment stones, and contraindication in obstructive cholestasis and acute cholecystitis.
Parent: Ursodiol /Ursodeoxycholic Acid
Pharmaceutical grade ursodiol is characterized and controlled for related bile acid impurities, epimers, process-related residues, and residual solvents using validated chromatographic and spectroscopic methods such as HPLC, LC MS, and GC for volatile solvents. Typical related bile acid impurities include chenodeoxycholic acid, deoxycholic acid, lithocholic acid, and various stereoisomers and epimers of ursodeoxycholic acid. Typical specification ranges used by manufacturers and pharmacopeial monographs are presented as ranges to reflect accepted industry practice: individual specified related substances commonly limited to 0.1 to 0.5 percent by weight each, unspecified individual impurities limited to 0.05 to 0.2 percent, and total related substances often limited to 1.0 to 2.0 percent. Residual solvents and heavy metals are controlled to pharmacopeial limits and the assay potency of the active ingredient is typically specified in the high nineties percent range for UDCA, for example commonly in the range of 98.0 to 101.0 percent on an anhydrous basis depending on the supplier or monograph.
Ursodiol is used to dissolve cholesterol gallstones in selected patients who cannot or choose not to undergo surgery and to prevent gallstone formation in people undergoing rapid weight loss; it is also used in certain cholestatic liver diseases to improve bile flow and reduce liver injury.
Ursodiol reduces cholesterol saturation of bile by decreasing hepatic cholesterol secretion and intestinal cholesterol absorption, increases solubilization of cholesterol in bile by replacing hydrophobic bile acids in the bile acid pool, and exerts cytoprotective effects on hepatocytes and cholangiocytes that reduce bile acid induced cell injury.
Chemically ursodiol is a bile acid derived from the steroidal cholesterol backbone so it is a steroidal molecule by structure, but it is not a steroid hormone and does not act as a corticosteroid or anabolic steroid; it functions as a bile acid with detergent and cytoprotective properties.
Physicians may not prescribe ursodiol for many patients because it only dissolves noncalcified cholesterol stones of limited size and requires months to years of therapy with a substantial recurrence rate, it is ineffective for pigment or calcified stones and in the presence of biliary obstruction, and surgical cholecystectomy remains the definitive and faster treatment for symptomatic gallstone disease; safety, cost, availability, and specific contraindications also influence prescribing decisions.
