Dose equivalency evaluation of major corticosteroids: pharmacokinetics and cell trafficking and cortisol dynamics.
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.
Mager
Donald E
DE
Buffalo Clinical Research Center, Buffalo, NY, USA.
Lin
Sheren X
SX
Blum
Robert A
RA
Lates
Christian D
CD
Jusko
William J
WJ
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000328:Adult; D000704:Analysis of Variance; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D016014:Linear Models; D008214:Lymphocytes / Q000097:blood / Q000166:cytology / Q000187:drug effects*; D008297:Male; D016037:Single-Blind Method; D013810:Therapeutic Equivalency
D000305:Adrenal Cortex Hormones; D006854:Hydrocortisone