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

Prednisone and Prednisolone: Equivalence and Usage

Prednisone and prednisolone are therapeutically equivalent medications that are used interchangeably at the same dosage, with the primary difference being that prednisone requires hepatic conversion to its active form (prednisolone), while prednisolone is already in its active form. 1

Pharmacological Equivalence

Both medications are considered completely equivalent in clinical practice and can be substituted for one another at identical doses. 1 This equivalence has been explicitly stated in multiple international guidelines:

• KDIGO guidelines specifically note 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
• All references to prednisone in major nephrology guidelines apply equally to prednisolone 1
• The choice between the two typically depends on country of origin and local availability rather than clinical superiority 1

Key Pharmacological Differences

Metabolism and Bioavailability

• Prednisone is a prodrug that requires hepatic conversion via 11β-hydroxysteroid dehydrogenase to become active prednisolone 2
• Prednisolone is already in its active form and does not require hepatic conversion 3
• Despite this difference, the interconversion of prednisone to prednisolone is not a limiting factor, even in patients with severely impaired liver function 2
• Prednisolone oral solution produces a 14% higher peak plasma level that occurs 20% faster than tablets 3

Clinical Implications of Metabolic Differences

The hepatic conversion requirement has minimal clinical impact in most situations:

• Even patients with severe liver dysfunction adequately convert prednisone to prednisolone 2
• There is no need to preferentially use prednisolone over prednisone in liver disease 2
• The only theoretical advantage of prednisolone would be in cases of complete hepatic failure, though this is rarely clinically relevant 2

Dosing Principles (Applicable to Both)

Standard Dosing Ranges

• Initial dosing ranges from 5-60 mg per day depending on the disease being treated 4
• For nephrotic syndrome: 1 mg/kg daily (maximum 80 mg) or 2 mg/kg alternate-day (maximum 120 mg) 1
• For FSGS: same dosing as nephrotic syndrome 1
• For vasculitis: dosing varies but typically starts at 1 mg/kg/day 1

Timing of Administration

Single daily dosing should be administered in the morning prior to 9 AM to minimize adrenal suppression 4, as this aligns with the body's natural cortisol rhythm when maximal adrenal activity occurs between 2 AM and 8 AM 4.

Tapering Considerations

• Initial tapering should aim to reduce to 10 mg/day within 4-8 weeks 5
• Once below 10 mg, slower tapering at 1 mg every 4 weeks is recommended to minimize adrenal insufficiency risk 5
• Never abruptly discontinue after long-term therapy; gradual withdrawal is essential 4

Common Pitfalls to Avoid

Assuming Prednisolone is Superior in Liver Disease

This is a common misconception. While prednisolone is the active form, prednisone conversion remains adequate even in severe hepatic impairment 2. The choice should be based on availability and cost rather than liver function in most cases.

Incorrect Dose Equivalence Assumptions

Do not confuse prednisone/prednisolone equivalence with other corticosteroids. For example, betamethasone 1 mg is approximately equivalent to prednisolone 8 mg, and betamethasone causes significantly more adrenal suppression at equivalent anti-inflammatory doses 6. Prednisone and prednisolone, however, are truly 1:1 equivalent 1.

Divided Dosing Without Indication

Single daily morning dosing is preferred over divided doses 5, 4 except in specific situations requiring multiple daily doses 4. Divided dosing increases the risk of HPA axis suppression by maintaining elevated corticosteroid levels throughout the 24-hour cycle 4.

Geographic Prescribing Patterns

The choice between prednisone and prednisolone often reflects geographic prescribing patterns rather than clinical superiority:

• Prednisone is more commonly used in the United States 1
• Prednisolone is more commonly used in Europe and other regions 1
• Both have been used successfully in randomized controlled trials 1

Special Populations

Elderly Patients

• Elderly patients have higher total and unbound prednisolone concentrations due to impaired metabolic clearance 3
• Despite higher drug levels, elderly patients show less suppression of endogenous cortisol 3
• Dose adjustments are generally not required, but monitoring for adverse effects is important 3

Patients with Altered Protein Binding

Hypoproteinemia per se does not cause increased unbound concentrations of prednisolone in vivo 2, contrary to what might be expected from basic pharmacology principles. However, certain conditions do alter prednisolone pharmacokinetics:

• Increased unbound concentrations occur in: liver failure, renal failure, renal transplant recipients, elderly patients, women on oral contraceptives, and patients taking ketoconazole 2
• Decreased concentrations occur in: hyperthyroid patients, some Crohn's disease patients, and those taking enzyme-inducing agents 2