What is the preferred choice between prednisolone and prednisone (corticosteroids) for treatment?

Prednisone vs. Prednisolone: Clinical Selection Guidelines

In patients with normal liver function, prednisone and prednisolone can be used interchangeably at equivalent doses, as they have identical potency, duration of action, and side effect profiles. However, prednisolone is preferred in patients with significant liver disease due to impaired conversion of prednisone to its active form in hepatic dysfunction. 1

Pharmacological Considerations

Mechanism and Equivalence

• Prednisone is a prodrug that requires hepatic conversion to prednisolone (the active form)
• 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 1

Conversion in Liver Disease

• Patients with liver cirrhosis show impaired conversion of prednisone to prednisolone 2
• In severe liver dysfunction, serum prednisolone concentration after oral prednisone may be only 53% of that observed in patients with mild liver dysfunction 2
• Mean serum prednisolone after oral prednisolone administration remains independent of liver function 2

Clinical Decision Algorithm

Use Prednisolone When:

• Patient has significant liver disease/cirrhosis 3, 2
• Patient has severe active hepatocellular necrosis 4
• Patient requires predictable plasma levels (prednisolone provides less variable plasma levels) 4
• Patient has hypoalbuminemia (decreased protein binding of prednisolone occurs, requiring dose adjustment) 1, 5

Use Prednisone When:

• Patient has normal liver function 1
• Local availability or cost favors prednisone 1
• Patient preference regarding formulation favors prednisone 1

Special Considerations

Liver Disease

• Advanced cirrhosis can impair the conversion of prednisone to prednisolone, but this impairment is generally insufficient to alter treatment response in most cases of autoimmune hepatitis 3
• However, in severe liver dysfunction, prednisolone is preferred to ensure therapeutic efficacy 2
• Patients with hypoalbuminemia may experience higher free (unbound) prednisolone levels, potentially increasing side effects 1, 5

Dosing in Specific Conditions

• Autoimmune hepatitis: 60 mg/day as monotherapy or 30 mg/day with azathioprine 3, 1
• Alcoholic hepatitis: Prednisolone 40 mg daily for 4 weeks, then tapered over 2-4 weeks 3
• Acute severe autoimmune hepatitis: Prednisone or prednisolone alone (0.5-1 mg/kg daily in adults, up to 2 mg/kg in children) 3

Practical Considerations

Bioavailability

• In patients with normal liver function, bioavailability is linearly related to the dose of prednisone 6
• Oral prednisone bioavailability approximates 100% of an intravenous dose in both healthy individuals and those with chronic active liver disease 6

Monitoring

• In patients with liver disease, plasma prednisolone levels may be more variable after either drug 4
• Consider monitoring plasma levels in patients whose disease cannot be controlled by normal maintenance doses 4

Side Effects

• Both medications have identical side effect profiles at equivalent doses 1
• Common side effects include hypertension, glucose intolerance, weight gain, decreased bone density, adrenal suppression, and emotional lability 1
• 80% of patients develop cosmetic changes (facial rounding, acne, dorsal hump, truncal obesity) after two years of corticosteroid therapy 3
• Severe complications (osteoporosis, vertebral compression, diabetes, cataracts, hypertension, psychosis) typically develop after 18 months of continuous therapy at doses exceeding 10 mg daily 3

Conclusion

While both medications are pharmacologically equivalent in patients with normal liver function, prednisolone offers more predictable therapeutic levels in patients with liver disease and eliminates the concern about impaired conversion from prednisone.