URSODIOL

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Ursodiol is a hydrophilic bile acid that reduces the concentration of hydrophobic bile acids, thereby decreasing cholesterol secretion into bile and promoting dissolution of cholesterol gallstones. It also exerts cytoprotective effects on hepatocytes by stabilizing cell membranes and reducing apoptosis in cholestatic liver diseases.

What the body does with it

Metabolism	Undergoes enterohepatic circulation; conjugated with glycine or taurine in the liver and secreted into bile; small fraction is deconjugated by intestinal bacteria and converted to lithocholic acid, which is sulfated and excreted.
Excretion	Primarily fecal (biliary excretion of unchanged drug and metabolites); minimal renal excretion (<1% unchanged in urine).
Half-life	Terminal elimination half-life: 3.5–5.8 days for endogenous bile acids; for exogenous ursodiol, half-life is approximately 4–6 days, reflecting slow turnover of bile acid pool.
Protein binding	Approximately 96–98% bound to plasma proteins, primarily albumin.
Volume of Distribution	Volume of distribution: 0.3–0.5 L/kg; indicates distribution largely within extracellular fluid and bile; low Vd consistent with high protein binding and limited tissue penetration.
Bioavailability	Oral bioavailability: Approximately 30–60% after oral administration due to extensive first-pass hepatic clearance; absorption occurs in the small intestine, and absorbed drug is efficiently extracted by the liver.
Onset of Action	Oral: Clinical effects (e.g., improvement in liver enzymes, gallstone dissolution) observed after several weeks (4–8 weeks); maximal effect may take 6–24 months for gallstone dissolution.
Duration of Action	Duration of action: Not well defined due to long-term therapy; effect persists as long as drug is taken; after discontinuation, bile acid composition returns to pretreatment levels over several weeks.

Classification & Brands

Dosing & administration

13-15 mg/kg/day orally divided into 2-4 doses for cholesterol gallstones; 13-15 mg/kg/day orally divided into 2-4 doses for primary biliary cholangitis.

Dosage form	CAPSULE
Renal impairment	No specific dose adjustment recommended; use caution in severe renal impairment (eGFR <30 mL/min) due to limited data.
Liver impairment	Child-Pugh Class A: No adjustment. Child-Pugh Class B or C: Not recommended; consider alternative therapy.
Pediatric use	For cholestatic liver disease: 10-15 mg/kg/day orally divided into 2-3 doses; maximum 15 mg/kg/day.
Geriatric use	No specific adjustment required; monitor renal function and for adverse effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Aluminum-based antacids and cholestyramine may reduce absorption Generally well-tolerated with diarrhea being the most common side effect.

Breastfeeding	Ursodiol is excreted into human breast milk in low amounts. The milk-to-plasma ratio is approximately 0.1. It is considered compatible with breastfeeding when used for maternal indications.
Teratogenic Risk	Ursodiol is not associated with an increased risk of major congenital malformations based on human data. In animal studies, no teratogenicity was observed at clinically relevant doses. Fetal risk in all trimesters is considered low.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Common Effects	primary biliary cholangitis
Serious Effects

Absolute Contraindications

Hypersensitivity to ursodiol or any component; complete biliary obstruction; chronic liver disease with ascites or varices (relative).

Clinical Precautions

Precautions

May cause diarrhea, constipation, nausea, vomiting, dyspepsia; use with caution in patients with pre-existing liver disease or biliary obstruction; not recommended for calcified gallstones or radiopaque stones; monitor liver function tests periodically.

Clinical Tips & Counseling

Drug interactions

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