Prednisone, a glucocorticoid, undergoes extensive first-pass metabolism in the liver, primarily converting to its active form, prednisolone. This process significantly impacts its bioavailability, which averages around 80%.
Absorption and Distribution
Oral prednisone absorption is rapid and near-complete, with peak plasma concentrations typically observed within 1-2 hours of ingestion. Food may slightly delay absorption. Prednisolone, the active metabolite, distributes widely throughout the body, crossing the blood-brain barrier and placental barrier. Protein binding is substantial (approximately 77-90%), impacting drug distribution and duration.
Metabolism and Excretion
- Prednisone’s primary metabolic pathway involves reduction to prednisolone via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Prednisolone is further metabolized through glucuronidation and sulfation. Renal excretion accounts for the majority (approximately 60%) of prednisolone elimination, with a smaller portion excreted in feces. The elimination half-life of prednisolone ranges from 3-20 hours, influenced by factors such as hepatic and renal function.
Factors Affecting Pharmacokinetics
Liver Function: Impaired liver function can reduce the conversion of prednisone to prednisolone, affecting efficacy. Kidney Function: Reduced renal clearance prolongs prednisolone’s elimination half-life, potentially leading to drug accumulation. Drug Interactions: Certain medications, such as CYP3A4 inhibitors or inducers, can influence prednisolone metabolism and plasma concentrations. Age: Older adults might experience altered pharmacokinetics due to changes in hepatic and renal function.
Clinical Implications
Understanding prednisone’s pharmacokinetics guides optimal dosing strategies and anticipates potential drug interactions. Dosage adjustments might be necessary for patients with impaired hepatic or renal function. Monitoring for adverse effects is crucial, particularly during long-term therapy. Close observation for signs of adrenal suppression is also imperative.
Individual Variation
Significant inter-individual variability exists in prednisone metabolism. Genetic factors and concomitant medications contribute to this variation, highlighting the importance of individualized treatment approaches and careful patient monitoring.
