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Dose Equivalency Evaluation of Major Corticosteroids: Pharmacokinetics and Cell Trafficking and Cortisol Dynamics

From the Buffalo Clinical Research Center, Buffalo, New York (Dr. Lin, Dr. Blum, Dr. Lates) and the Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York (Dr. Mager, Dr. Jusko).

The integrity of current corticosteroid dose equivalency tables, as assessed by mechanistic models for cell trafficking and cortisol dynamics, was investigated in this study. Single, presumably equivalent, doses of intravenous hydrocortisone, methylprednisolone, dexamethasone, and oral prednisolone were given to 5 white men, according to total body weight, in a 5-way crossover, placebo-controlled study. Pharmacodynamic (PD) response-time profiles for T helper cells, T suppressor cells, neutrophils, and adrenal suppression were evaluated by extended indirect response models. For adrenal suppression, prednisolone appears to be less potent than methylprednisolone or dexamethasone. A good correlation was found between the estimated in vivo EC₅₀ values and relative receptor affinity (equilibrium dissociation constants normalized to dexamethasone). Area under the effect curves of all PD responses was calculated using a linear-trapezoidal method. Although T helper cell trafficking and adrenal suppression achieved significant differences by repeated-measures ANOVA (p = 0.014 and 0.022), post hoc analysis using the Bonferroni method revealed no difference between treatments. Although limited by the use of single doses and a relatively small sample size, this study applies mechanistic models for several biomarkers showing that currently used dosing tables reflect reasonable dose equivalency relationships for four corticosteroids.

Key Words: Glucocorticosteroids • dose equivalency tables • cell trafficking • pharmacokinetics

Address for reprints: William J. Jusko, PhD, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14260.

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