Prednisolone clearance at steady state in man

Area of Science:

• Pharmacology
• Clinical Pharmacokinetics

Background:

• Prednisolone is a widely used corticosteroid.
• Understanding its pharmacokinetic profile is crucial for optimizing therapeutic efficacy and minimizing adverse effects.

Purpose of the Study:

• To investigate the dose-dependent kinetics of prednisolone in healthy volunteers.
• To determine the influence of dose on prednisolone clearance, protein binding, and interconversion with prednisone.

Main Methods:

• Administered prednisolone via intravenous infusion at two different rates (low and high dose) to ten healthy volunteers.
• Measured steady-state plasma concentrations of total and unbound prednisolone, as well as prednisone.
• Calculated pharmacokinetic parameters including clearance and protein binding fraction.

Main Results:

• Prednisolone exhibited a 5-fold increase in steady-state levels with a 12-fold increase in infusion rate, indicating dose-dependent clearance.
• The fraction of unbound prednisolone doubled with increasing dose, suggesting saturable protein binding.
• Apparent clearance of unbound prednisolone increased slightly with dose, influenced by interconversion with prednisone.

Conclusions:

• Prednisolone displays dose- and concentration-dependent pharmacokinetics in humans.
• Saturable protein binding is the primary driver of these observed kinetic changes.
• Interconversion with prednisone complicates the interpretation of unbound prednisolone clearance.