What are the pharmacokinetics of Prednisone (corticosteroid)?

From the Guidelines

Prednisone is a synthetic glucocorticoid with intermediate-acting properties that undergoes hepatic metabolism to its active form, prednisolone, with a recommended daily dose of ≤7.5 mg/day to minimize long-term detrimental effects 1.

Pharmacokinetics

The drug is rapidly absorbed from the gastrointestinal tract with peak plasma concentrations occurring within 1-2 hours.

• It has good bioavailability (70-80%) and is extensively bound to plasma proteins (90%), primarily albumin.
• Prednisone has a plasma half-life of 2-4 hours, while its active metabolite prednisolone has a biological half-life of 12-36 hours, which explains its clinical duration of action.
• The drug is primarily metabolized in the liver through reduction and conjugation, with subsequent elimination occurring mainly through renal excretion.

Factors Affecting Pharmacokinetics

Factors affecting prednisone pharmacokinetics include:

• Liver function, as hepatic impairment can prolong its half-life
• Renal function, which impacts clearance
• Concurrent medications that may induce or inhibit hepatic enzymes

Clinical Considerations

The medium to long-term aim should be to minimize daily dose to ≤7.5 mg/day prednisone equivalent or to discontinue them, because long-term GC therapy can have various detrimental effects including irreversible organ damage 1. Prednisone follows linear pharmacokinetics at therapeutic doses, meaning plasma concentrations increase proportionally with dose increases.

• The drug readily crosses cell membranes due to its lipophilic nature and can cross the placenta and appear in breast milk, requiring careful consideration during pregnancy and lactation.
• High-dose intravenous methylprednisolone (usually 250–1000 mg/day for 3 days) is often used in acute, organ-threatening disease (eg, renal, neuropsychiatric) excluding infections 1.

From the FDA Drug Label

Prednisolone is rapidly and well absorbed from the gastrointestinal tract following oral administration. Prednisolone sodium phosphate oral solution produces a 14% higher peak plasma level of prednisolone which occurs 20% faster than that seen with tablets. Prednisolone is 70–90% protein-bound in the plasma and it is eliminated from the plasma with a half-life of 2 to 4 hours It is metabolized mainly in the liver and excreted in the urine as sulfate and glucuronide conjugates.

The pharmacokinetics of prednisone (note: the label is for prednisolone) are not directly addressed in the label, but we can infer some information about its pharmacokinetics from the information about prednisolone.

• Absorption: The label does not provide information about the absorption of prednisone.
• Distribution: The label does not provide information about the distribution of prednisone.
• Metabolism: The label does not provide information about the metabolism of prednisone.
• Elimination: The label does not provide information about the elimination of prednisone. However, the label does mention that interconversion between prednisolone and prednisone occurs 2. Since the label does not directly address the question about prednisone pharmacokinetics, no conclusion can be drawn.

From the Research

Pharmacokinetics of Prednisone

• Prednisone is effectively absorbed and converted to its active therapeutic derivative, prednisolone, in healthy volunteers and in patients with liver disease 3
• The bioavailability of oral prednisone approximates 100% of an intravenous dose and is comparable after administration of either prednisone or prednisolone 3
• However, another study found that the bioavailability of prednisone was about 62% after an oral dose of 0.8 mg kg-1 4
• Patients with liver disease and hypoalbuminaemia are more likely to suffer major side effects of prednisone as a consequence of decreased protein binding and delayed clearance of prednisolone 3

Metabolism and Interconversion

• There is a high degree of interconversion between prednisone and prednisolone, with 76% of the dose being recycled 4
• The formation clearance of prednisolone from prednisone is much greater than the formation clearance of prednisone from prednisolone or the irreversible elimination clearances of the two steroids 4

Factors Affecting Pharmacokinetics

• The pharmacokinetics of prednisone and prednisolone can be affected by various factors, including liver disease, kidney disease, and other drugs 5
• The use of antacids, food, and other drugs can also affect the bioavailability of prednisone and prednisolone 5

Clinical Implications

• Dosage of prednisone should be reduced in patients with liver disease and hypoalbuminaemia in accordance with serum albumin concentration 3
• Low doses of prednisone or prednisolone can control most of the inflammatory features of early polyarticular rheumatoid arthritis, and can also retard the bony damage of rheumatoid arthritis 6