Volume 43, Issue 11 p. 1216-1227

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

Dr. Donald E. Mager PharmD, PhD

Dr. Donald E. Mager PharmD, PhD

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York

Search for more papers by this author
Dr. Sheren X. Lin PharmD

Dr. Sheren X. Lin PharmD

Buffalo Clinical Research Center, Buffalo, New York

Dr. Jusko from the National Institutes of General Medical Sciences (National Institutes of Health); fellowship support for Dr. Lin from GlaxoSmithKline Pharmaceuticals, Philadelphia; and a predoctoral fellowship for Dr. Mager from the American Foundation for Pharmaceutical Education.

Search for more papers by this author
Dr. Robert A. Blum PharmD

Dr. Robert A. Blum PharmD

Buffalo Clinical Research Center, Buffalo, New York

Search for more papers by this author
Dr. Christian D. Lates MD

Dr. Christian D. Lates MD

Buffalo Clinical Research Center, Buffalo, New York

Search for more papers by this author
Dr. William J. Jusko PhD

Corresponding Author

Dr. William J. Jusko PhD

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, New York

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 14260Search for more papers by this author
First published: 08 March 2013
Citations: 120

Abstract

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.