ursodiol

Brand: Actigall, Urso

Prototype Drug
Drug Class: bile acid
Drug Family: GI agent
Subclass: hydrophilic bile acid (ursodeoxycholic acid — UDCA)
Organ Systems: gastrointestinal

Mechanism of Action

Naturally occurring hydrophilic bile acid; replaces toxic hydrophobic bile acids in bile pool reducing cholesterol saturation; hepatoprotective by protecting against hydrophobic bile acid cytotoxicity.

hepatocyte bile acid composition

Indications

  • gallstone dissolution (small cholesterol stones)
  • primary biliary cholangitis (PBC)
  • NAFLD/NASH (uncertain benefit)
  • prophylaxis during rapid weight loss or bariatric surgery
  • primary sclerosing cholangitis (limited benefit)

Contraindications

  • bile duct obstruction
  • complete biliary obstruction
  • calcified/radiopaque gallstones
  • allergy

Adverse Effects

Common

  • diarrhea
  • GI upset
  • hepatotoxicity (rare — paradoxical)

Serious

  • hepatotoxicity (advanced liver disease — paradoxical worsening in severe cirrhosis)

Pharmacokinetics (ADME)

Absorption ~90% absorbed
Distribution moderate
Metabolism hepatic first-pass
Excretion biliary (enterohepatic recirculation)
Half-life 2.5-5 days
Onset varies
Peak 1-3 hours
Duration months to years
Protein Binding none
Vd moderate

Drug Interactions

Drug / Agent Mechanism Severity
cholestyramine/antacids reduce UDCA absorption — separate by 2 hours moderate
estrogens/clofibrate increase biliary cholesterol secretion counteracting UDCA effect moderate

Nursing Considerations

  1. PBC: monitor LFTs; treatment must be continued indefinitely
  2. Gallstone dissolution: requires months to years; stones must be radiolucent (cholesterol, not calcium)
  3. Separate from cholestyramine by 2 hours (reduced absorption)

Clinical Pearls

  • Gallstone dissolution: UDCA reduces cholesterol saturation by 30-40%; recurrence after discontinuation is common
  • PBC: reduces LFTs and slows disease progression but does not normalize liver histology in all patients

Safety Profile

Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required