What is the difference between prednisone and prednisolone in terms of therapeutic effects and usage?

Prednisone vs. Prednisolone: Therapeutic Effects and Usage

Prednisone and prednisolone are therapeutically equivalent in patients with normal liver function, but prednisolone is preferred in patients with liver disease as it does not require hepatic conversion to become active.

Pharmacological Differences

• Conversion Process: Prednisone is a prodrug that requires hepatic conversion to its active form, prednisolone 1
• Bioavailability: Prednisolone sodium phosphate produces approximately 14% higher peak plasma levels that occur 20% faster than prednisone tablets 2, 1
• Protein Binding: Prednisolone is 70-90% protein-bound in plasma with a half-life of 2-4 hours 1
• Elimination: Both are metabolized mainly in the liver and excreted in urine as sulfate and glucuronide conjugates 1

Clinical Equivalence

In patients with normal liver function:

• Both medications have similar overall bioavailability 2
• Guidelines explicitly state that "prednisone and prednisolone are equivalent, are used in the same dosage, and have both been used in randomized controlled trials depending on the country of origin" 3
• The KDIGO guidelines for glomerulonephritis specifically note that references to prednisone also refer to prednisolone 3

Special Considerations for Liver Disease

• Patients with active hepatocellular necrosis show evidence of impaired activation of prednisone to prednisolone 4
• The American Association for the Study of Liver Diseases recommends prednisolone over prednisone in patients with significant liver disease 2
• However, research indicates that the interconversion of prednisone into prednisolone is not a limiting factor, even in patients with severely impaired liver function 5
• A study of patients with chronic active liver disease found no significant differences in pharmacokinetics between prednisone and prednisolone, suggesting either medication is effective 6

Dosing Considerations

Standard dosing regimens include:

• Glomerulonephritis: 60 mg/day or 2 mg/kg/day (maximum 60 mg/day) for 4-6 weeks, followed by alternate-day medication at 40 mg/m² or 1.5 mg/kg 3
• Autoimmune Hepatitis: 60 mg/day as monotherapy or 30 mg/day with azathioprine 3
• Sudden Hearing Loss: 1 mg/kg/day (maximum 60 mg daily) for 10-14 days, followed by tapering 3

Side Effects

Both medications have identical side effect profiles when equivalent doses are used 2:

• Hypertension
• Glucose intolerance
• Weight gain
• Decreased bone density
• Adrenal suppression
• Emotional lability

Clinical Decision-Making Algorithm

1. For patients with normal liver function:

   • Either medication can be used interchangeably at the same dose
   • Consider prednisolone if faster onset of action is desired (14% higher peak levels, 20% faster)

2. For patients with liver disease:

   • Prefer prednisolone, especially with active hepatocellular necrosis
   • If using prednisone, monitor response carefully as conversion may be variable

3. For patients with hypoalbuminemia:

   • Consider dose reduction due to decreased protein binding and delayed clearance of prednisolone 7
   • Monitor for increased side effects

4. For long-term therapy:

   • Consider alternate-day dosing to reduce side effects
   • Taper slowly to avoid adrenal insufficiency

Common Pitfalls to Avoid

1. Underdosing: Ensure equivalent potency when switching between corticosteroids. For example, prednisone 60 mg equals methylprednisolone 48 mg or dexamethasone 10 mg 3

2. Abrupt discontinuation: Always taper corticosteroids to avoid adrenal insufficiency

3. Overlooking liver function: Failure to consider hepatic conversion of prednisone in patients with liver disease may result in unpredictable therapeutic effects 4

4. Ignoring protein binding: In hypoalbuminemic states, free prednisolone levels may be higher, potentially increasing side effects 7