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Cortisol does not inhibit prednisolone clearance.

P J Meffin, B C Sallustio, Y J Purdie

    British Journal of Clinical Pharmacology
    |October 1, 1985
    PubMed
    Summary
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    Cortisol administration significantly alters how the body processes prednisolone, increasing its total clearance and distribution volume. However, the clearance of unbound prednisolone remains unchanged, indicating specific metabolic pathways are affected.

    Area of Science:

    • Pharmacokinetics
    • Endocrinology
    • Drug Metabolism

    Background:

    • Prednisolone is a widely used corticosteroid with significant inter-individual variability in disposition.
    • Cortisol, the primary endogenous glucocorticoid, shares metabolic pathways with exogenous corticosteroids.
    • Understanding drug interactions is crucial for optimizing corticosteroid therapy.

    Purpose of the Study:

    • To investigate the pharmacokinetic disposition of prednisolone.
    • To determine the effect of exogenous cortisol administration on prednisolone pharmacokinetics in healthy male subjects.

    Main Methods:

    • Eight healthy male subjects participated in the study.
    • Prednisolone disposition was assessed with and without concomitant cortisol administration.

    Related Experiment Videos

  • Plasma cortisol levels were elevated 10-fold above endogenous levels during co-administration.

    • Main Results:

    • Total prednisolone clearance and steady-state distribution volume were significantly increased by cortisol co-administration.
    • The free fraction of prednisolone in plasma also increased.
    • Crucially, the clearance of unbound prednisolone remained unaltered by the presence of high cortisol levels.

    Conclusions:

    • Exogenous cortisol administration alters the disposition of total prednisolone, likely through effects on protein binding or metabolic pathways affecting the bound fraction.
    • The unchanged clearance of unbound prednisolone suggests that the core metabolic clearance of the active drug form is not directly impacted by elevated cortisol levels.