Generic Name

Ursodeoxycholic acid

Mechanism

• Reduces cholesterol solubility in bile by replacing toxic bile acids with the hydrophilic ursodeoxycholic acid.
• Inhibits cholesterol micelle formation → ↓ nucleation & aggregation of cholesterol crystals.
• Stimulates bile flow and protects hepatocyte membranes from bile acid toxicity.
• Promotes enterohepatic circulation, allowing repeated use of the drug within the intestine.

Pharmacokinetics

• Absorption: 30–65 % orally; 20 % higher when taken with food.
• Bioavailability: ~50 % due to hepatic first‑pass glucuronidation.
• Metabolism: conjugated (glucuronide, sulfate) primarily in the liver.
• Excretion: 90 % into bile, 10 % renal; hepatic transporters (OATP1B1/3) are critical.
• Half‑life: 8–10 h; terminal phase prolonged by enterohepatic recycling.

Indications

• Cholesterol gallstone dissolution (selected patients with < 3 cm stones).
• Prevention of gallstone recurrence after cholecystectomy.
• Primary biliary cholangitis (as adjunct in cholestasis).
• Bariatric‑surgery prophylaxis (to reduce post‑operative gallstone risk).
• Idiopathic cholestatic liver disease (infants or adults).
• Conservative management of mild gallstone pancreatitis (small impacted stones).

Contraindications

• Choledocholithiasis / biliary obstruction (unless surgery planned).
• Known hypersensitivity to ursodeoxycholic acid or excipients.
• Severe hepatic impairment—use cautiously; limit dose.
• Pregnancy: Category B; use only if benefits > risks.
• Breastfeeding: excreted in milk; counsel patient.

Dosing

• Take with meals to enhance absorption.
• Monitor LFTs; if ALP < 1.5 × ULN after 6 mo, consider dose reduction.

Adverse Effects

Management: Discontinue immediately if signs of hepatic injury (jaundice, markedly ↑LFTs).

Monitoring

• Baseline + every 4–6 weeks: AST, ALT, ALP, total bilirubin.
• Renal function: Cr/ BUN if renal disease present.
• Ultrasound: baseline, then every 6–12 mo (stone dissolution or recurrence).
• Symptom diary: GI upset, pruritus, rash.

Clinical Pearls

• Combination therapy: Adding *ezetimibe* reduces hepatic cholesterol production, accelerating stone dissolution.
• Dose splitting: Taking divided doses around meals maximizes enterohepatic cycling and efficacy.
• Titration guard rails: Begin at 300–600 mg/day to reduce GI intolerance, then increase to 1–2 g/day only after tolerance.
• Myopathy vigilance: Do not co‑administer with statins unless patients are under close monitoring or the statin has a lower myopathy risk profile.
• Prophylaxis advantage: A 12‑month regimen after cholecystectomy lowers gallstone recurrence by ~45 % in high‑risk groups (e.g., patients with hyperlipidemia or rapid weight loss).
• Pregnancy safety: Though Category B, if the patient becomes pregnant during therapy, consider continuing only if clinically warranted and discuss risks.

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• Key pharmacology terms: *ursodeoxycholic acid, bile acid therapy, cholesterol gallstones, hepatobiliary, enterohepatic circulation, cholestasis*.