Which is stronger, methylprednisolone or prednisone?

Methylprednisolone vs Prednisone: Comparative Potency

Methylprednisolone is approximately 1.25 times more potent than prednisone on a milligram-per-milligram basis, meaning 4 mg of methylprednisolone equals approximately 5 mg of prednisone. 1, 2

Relative Potency Comparison

Both methylprednisolone and prednisone are intermediate-acting corticosteroids that are 4-5 times more potent than hydrocortisone, placing them in the same general potency class. 3 However, when directly compared:

• Prednisone 60 mg = Methylprednisolone 48 mg 1
• Prednisone 5 mg = Methylprednisolone 4 mg 2
• This translates to a 1.25:1 conversion ratio (prednisone:methylprednisolone) 1

Clinical Pharmacokinetic Advantages of Methylprednisolone

While the anti-inflammatory potency difference is modest, methylprednisolone demonstrates several pharmacokinetic advantages that may translate to clinical benefits:

More Predictable Pharmacokinetics

• Methylprednisolone exhibits linear, dose-proportional pharmacokinetics with no dose or time dependency, making dosing more predictable 4
• Prednisolone shows marked dose-dependent clearance and volume of distribution due to saturable protein binding, making it "extremely difficult to determine the dose needed to obtain a desired target concentration" 4
• After multiple doses, prednisolone demonstrates time-dependent pharmacokinetics with increased clearance, further complicating dose predictions 4

Superior Tissue Penetration

• Methylprednisolone achieves significantly greater lung tissue concentrations than prednisolone due to a larger volume of distribution and longer mean residence time 5
• Methylprednisolone has a significantly longer plasma half-life and mean residence time compared to prednisolone 5
• By 90 minutes post-dose, plasma methylprednisolone concentrations remain significantly higher than prednisolone 5

Enhanced Lymphocyte Suppression in Specific Populations

• In healthy subjects, methylprednisolone demonstrates significantly higher lymphocyte-suppressive potency than prednisolone (IC50: 3.7 vs 19.4 ng/ml, p<0.01) 6
• In rheumatoid arthritis patients with high rheumatoid factor (>20 IU/ml) or RAPA (>80), methylprednisolone shows significantly greater lymphocyte suppression than prednisolone (p<0.05) 6

Clinical Equivalence in Most Inflammatory Conditions

Despite pharmacokinetic differences, clinical outcomes are generally equivalent when appropriate dose conversions are used:

• In lupus nephritis, pulse methylprednisolone (20 mg/kg) with low-dose prednisone achieved equivalent clinical and laboratory improvements compared to high-dose prednisone (2 mg/kg/day) with minimal side effects 7
• In rheumatoid arthritis patients overall, no significant difference in lymphocyte-suppressive potency was observed between the two drugs 6

Practical Prescribing Guidance

When to Choose Methylprednisolone

• Conditions requiring predictable, consistent dosing where dose-dependent pharmacokinetics of prednisone would complicate management 4
• Pulmonary conditions where enhanced lung tissue penetration may provide advantage 5
• Patients with high inflammatory markers (elevated RF or RAPA in rheumatoid conditions) where enhanced lymphocyte suppression may be beneficial 6
• Pulse therapy protocols where IV administration is planned, as methylprednisolone is the standard formulation 7

When Either Drug is Appropriate

• Most routine inflammatory conditions where the 1.25:1 conversion ratio can be applied 1, 2
• Bullous pemphigoid, polymyalgia rheumatica, and other standard indications where guidelines reference prednisone equivalents 8

Critical Dosing Conversions for Common Scenarios

• For immune checkpoint inhibitor toxicities: prednisone 1 mg/kg/day = methylprednisolone 0.8 mg/kg/day 1
• For polymyalgia rheumatica: prednisone 12.5-25 mg daily = methylprednisolone 10-20 mg daily 8, 1
• For bullous pemphigoid: prednisone 0.5 mg/kg daily = methylprednisolone 0.4 mg/kg daily 8, 1

Important Caveats

The standard Medrol dose pack (84 mg total methylprednisolone over 6 days) is substantially underdosed for most inflammatory conditions, providing only ~105 mg prednisone equivalent compared to the 540 mg typically needed for adequate anti-inflammatory effect in a 60 kg adult over 14 days. 9, 10 This common prescribing error leads to treatment failures that are incorrectly attributed to drug inefficacy rather than inadequate dosing.

Both drugs require identical bone protection measures: calcium and vitamin D supplementation with bisphosphonates for patients expected to take prednisone ≥7.5 mg daily (or methylprednisolone ≥6 mg daily) for ≥3 months. 8, 9