What is the difference between prednisone and prednisolone?

Prednisone vs. Prednisolone: Key Differences and Clinical Considerations

Prednisone and prednisolone are pharmacologically equivalent medications that can be used interchangeably in patients with normal liver function, with both administered at the same dosage. 1, 2

Pharmacological Relationship

• Prednisone is a prodrug that must be converted to prednisolone (the active form) in the liver
• Both medications have:
  • Identical potency (4× more potent than hydrocortisone)
  • Same equivalent dose (5 mg)
  • Similar intermediate duration of action (12-36 hours)
  • Identical side effect profiles at equivalent doses 2

Key Differences

Liver Disease Considerations

• In patients with liver disease or hepatic dysfunction, prednisolone is preferred over prednisone 2, 3
  • Prednisone requires hepatic conversion to become active prednisolone
  • Despite this theoretical concern, clinical studies show:
    • Patients with chronic active liver disease can effectively convert prednisone to prednisolone 4, 5
    • Serum concentrations suggest rapid interconversion equilibrium between the two corticosteroids 4
    • Treatment failure in liver disease is likely due to factors other than impaired prednisone metabolism 5

Protein Binding Considerations

• In patients with liver disease and hypoalbuminemia:
  • Decreased protein binding of prednisolone occurs
  • Delayed clearance of prednisolone may result
  • Higher risk of side effects due to increased free (unbound) prednisolone 3
  • Dosage reduction may be necessary based on serum albumin concentration 3

Clinical Guidelines and Usage

• KDIGO guidelines explicitly state that "prednisone and prednisolone are equivalent, used in the same dosage, and have both been used in randomized controlled trials depending on the country of origin" 1, 2
• For most conditions requiring corticosteroid therapy, either medication can be used at the same dosage:
  • Glomerulonephritis: 60 mg/day or 2 mg/kg/day (maximum 60 mg/day) 2
  • Autoimmune hepatitis: 60 mg/day as monotherapy or 30 mg/day with azathioprine 2
  • Inflammatory conditions: typically 40-60 mg daily with tapering 2

Practical Considerations

• Pharmacokinetic studies show that after administration of either drug:
  • Peak serum concentration and area under the curve for prednisolone are 4-5 times those of prednisone 4
  • Both medications achieve similar urinary concentrations 4
  • Interconversion between the two steroids occurs rapidly 6, 4

Clinical Recommendation

For most patients, the choice between prednisone and prednisolone can be based on:

1. Availability and cost in your region
2. Patient preference regarding formulation
3. Presence of liver disease (favor prednisolone if significant hepatic impairment)

The only significant clinical scenario where prednisolone should be specifically chosen over prednisone is in patients with severe liver dysfunction, although even this distinction may be less important than previously thought based on clinical studies 4, 5.