How do prednisone, prednisolone, methylprednisone, and methylprednisolone differ?

Key Differences Between Prednisone, Prednisolone, and Methylprednisolone

Prednisone and prednisolone are essentially interchangeable in clinical practice with identical anti-inflammatory potency (5 mg each), while methylprednisolone is 1.25 times more potent (4 mg methylprednisolone = 5 mg prednisone/prednisolone) and offers distinct pharmacological advantages including superior lung tissue penetration and minimal mineralocorticoid activity. 1, 2, 3

Note: "Methylprednisone" does not exist as a medication—this is a common naming error that should be avoided. 2

Standard Dose Equivalence

The fundamental conversion ratio used across all clinical contexts:

• Prednisone 5 mg = Prednisolone 5 mg = Methylprednisolone 4 mg 1, 2, 3
• This establishes a 1.25:1 ratio (prednisone:methylprednisolone) for all dose conversions 1, 2
• For example, prednisone 60 mg equals methylprednisolone 48 mg 1, 2

Pharmacological Distinctions

Bioavailability and Metabolism

• Prednisone is a prodrug that requires hepatic conversion to prednisolone (its active form) before exerting therapeutic effects 3
• Prednisolone is the active metabolite and does not require conversion, making it theoretically preferable in patients with severe liver dysfunction 3
• Both have excellent oral bioavailability (70-90% protein-bound), with prednisolone solution producing 14% higher peak plasma levels 20% faster than tablets 3
• Methylprednisolone does not require hepatic activation and is absorbed directly as the active compound 4, 5

Mineralocorticoid Activity

• Methylprednisolone has minimal to negligible mineralocorticoid activity at therapeutic doses, resulting in significantly less fluid retention, peripheral edema, and hypokalemia 1, 6
• Prednisone and prednisolone retain approximately 1/25th the mineralocorticoid activity of hydrocortisone, causing more sodium retention and potassium loss 1, 2
• When converting from hydrocortisone to methylprednisolone, potassium supplementation requirements typically decrease and monitoring is advised 1

Tissue Penetration and Duration

• Methylprednisolone demonstrates superior penetration into lung tissue with longer residence time, making it the preferred agent for ARDS and severe pulmonary inflammatory conditions 7
• Plasma elimination half-life is 2-4 hours for prednisolone and similar for methylprednisolone, though tissue effects persist much longer 3, 5
• The intermediate-acting classification applies to all three agents (versus short-acting hydrocortisone or long-acting dexamethasone) 8

Clinical Application Scenarios

Acute Respiratory Distress Syndrome (ARDS)

• Methylprednisolone is specifically recommended over prednisone/prednisolone for ARDS treatment 7
• Early ARDS (≤7 days): methylprednisolone 1 mg/kg/day 7
• Late ARDS (>6 days): methylprednisolone 2 mg/kg/day 7
• The superiority is attributed to enhanced lung tissue penetration and prolonged local anti-inflammatory effects 7

Perioperative Conversion

• When oral intake is restricted, prednisolone 30 mg oral = methylprednisolone 24 mg IV using the standard 1.25:1 ratio 1, 2
• Both routes maintain equivalent anti-inflammatory efficacy when dosed appropriately 1, 3

Immune-Mediated Conditions

• For grade 3-4 immune checkpoint inhibitor toxicity requiring hospitalization: IV methylprednisolone 1-2 mg/kg (equivalent to prednisone 1.25-2.5 mg/kg for subsequent oral therapy) 1, 2
• For polymyalgia rheumatica: prednisone 12.5-25 mg daily = methylprednisolone 10-20 mg daily 2
• For bullous pemphigoid: prednisone 0.5 mg/kg/day = methylprednisolone 0.4 mg/kg/day 2

Pregnancy Considerations

• Both prednisone and methylprednisolone cross the placenta minimally (only ~10% of maternal dose reaches fetus), making them preferred for treating maternal conditions during pregnancy 1
• Both are FDA pregnancy category B with no confirmed human teratogenicity 1
• Dexamethasone crosses more readily and is reserved for fetal indications 1

Adverse Effect Profile Differences

Fluid Retention and Electrolyte Disturbances

• Methylprednisolone causes significantly less peripheral edema, weight gain, and hypokalemia compared to prednisone/prednisolone due to minimal mineralocorticoid effects 1, 6
• This makes methylprednisolone preferable in patients with heart failure, cirrhosis, or baseline hypokalemia 6

Hyperglycemia

• All three agents cause comparable hyperglycemia at equivalent anti-inflammatory doses 7, 1
• Hyperglycemia is most pronounced in the first 36 hours following bolus dosing 7

Bone Protection Requirements

• Identical bone protection measures apply: patients receiving prednisone ≥7.5 mg daily (or methylprednisolone ≥6 mg daily) for ≥3 months require calcium, vitamin D, and bisphosphonate therapy 1, 2

Common Prescribing Pitfalls

Underdosing with Dose Packs

• The standard Medrol (methylprednisolone) dose pack provides only 84 mg total (≈105 mg prednisone-equivalent) over 6 days 1
• This is insufficient for most inflammatory conditions requiring full therapeutic dosing 1
• Full treatment for a 60 kg adult typically requires ~540 mg prednisone-equivalent over 14 days—more than 5 times the dose pack exposure 1

Inflammatory Marker Suppression

• ESR and CRP are markedly suppressed during active methylprednisolone therapy, rendering them unreliable for disease activity assessment 1
• Allow 1-2 weeks after completion before rechecking inflammatory markers 1

Tapering Requirements

• Methylprednisolone must be tapered slowly (6-14 days), not stopped abruptly, to prevent rebound inflammation from reconstituted inflammatory response 7
• Rapid discontinuation (2-4 days) or abrupt cessation may cause clinical deterioration 7

Repeat Dosing Intervals

• After completing a corticosteroid course, wait minimum 1-2 weeks before initiating another course in healthy patients 1
• Extend to 3-4 weeks in patients with diabetes, hypertension, osteoporosis, or glaucoma 1

Route-Specific Considerations

• All listed dose equivalencies apply only to oral or IV administration; intramuscular or intra-articular routes markedly alter relative potency 3
• Intramuscular methylprednisolone 120 mg every 3 weeks has been used as an alternative to daily oral regimens in rheumatic conditions with comparable efficacy 2

Practical Conversion Algorithm

When switching between agents:

1. Calculate the prednisone-equivalent dose of the current regimen
2. Apply the 1.25:1 ratio to convert to/from methylprednisolone (divide prednisone dose by 1.25 to get methylprednisolone dose) 1, 2
3. Consider clinical context: choose methylprednisolone for pulmonary conditions, fluid-sensitive states, or when mineralocorticoid effects are undesirable 7, 1, 6
4. Maintain equivalent anti-inflammatory dosing throughout the conversion 1, 2
5. Continue the same tapering schedule using the converted dose 7, 1