Ursodeoxycholic Acid – Hydrophilic Bile Acid Hepatoprotective Agent

Ursodeoxycholic Acid (UDCA) is a hydrophilic, non-toxic tertiary bile acid that exists as a natural minor component of human bile and is utilized as a systemic hepatoprotective, cholelitholytic, and anticholestatic therapeutic agent. The mechanism of action of ursodeoxycholic acid is multifactorial. Upon oral administration, UDCA competitively displaces toxic, hydrophobic endogenous bile acids (such as chenodeoxycholic, deoxycholic, and lithocholic acids) from the circulating bile acid pool within the intestines and liver, significantly reducing their enterohepatic circulation. By shielding the membranes of hepatocytes and cholangiocytes from the cytolytic actions of these toxic acids, UDCA inserts directly into the phospholipid bilayer of cellular membranes, stabilizing their structure and enhancing resistance against damaging agents. Its cholelitholytic efficacy is driven by a reduction in hepatic cholesterol synthesis, decreased intestinal cholesterol absorption, and a subsequent lowering of the lithogenic index of bile. This facilitates the progressive dissolution of cholesterol-based gallstones and prevents the formation of new calculi.

The clinical uniqueness of ursodeoxycholic acid lies in its established ability to delay the progression of fibrosis and histological deterioration in patients presenting with primary biliary cholangitis (PBC), markedly improving hepatic biochemical panels and prolonging transplant-free survival. The drug exerts potent immunomodulatory effects: it represses the pathological overexpression of HLA class I molecules on hepatocytes and HLA class II molecules on cholangiocytes, mitigating autoimmune targeting, and dampens cell apoptosis triggered by toxic bile acid exposure. Following oral intake, UDCA is rapidly and passively absorbed in the jejunum and ileum (approximately 60–80%). During its initial hepatic pass, up to 70% of the drug is extracted by hepatocytes and conjugated with glycine and taurine. With continuous dosing, UDCA becomes the predominant bile acid in the blood plasma, accounting for up to 30–50% of the total circulating pool. It undergoes bacterial biotransformation in the gut into lithocholic acid, which is largely excreted in the feces, while a small portion is absorbed, sulfated by the liver, and subsequently eliminated. The elimination half-life ranges from approximately 3.5 to 5.8 days. Systemic clearance occurs predominantly through the intestines in the feces.

The drug is administered orally. Initiating therapy for gallstone dissolution strictly requires prior confirmation of the cholesterol nature of the stones, their radiolucent characteristics, and the preservation of normal gallbladder function. Ongoing treatment requires regular liver function monitoring (ALT, AST, GGT, and bilirubin levels) alongside ultrasonographic or radiological assessments of the biliary tract executed every 6 months.