Pharmacoimmunodynamics of methylprednisolone: trafficking of helper T lymphocytes.
A two-compartment closed model was used to characterize the cell trafficking behavior of helper T cells in response to various single doses of methylprednisolone. Steroids are assumed to inhibit the circadian-determined cell return from extravascular sites to blood in a classic inhibitory pattern reflected by an IC50. The rate of cell efflux from tissues is modeled with a cosine function having a period of 24 hr and a maximum at about 1 AM. Nonlinear least-squares regression employing differential equations was used to analyze helper T-cell data from three human studies from our laboratory. The IC50 value of methylprednisolone of 12-19 ng/ml approximates receptor KD values. Simulations were performed to demonstrate the log-linear role of steroid dose or AUC on the integral of effect of helper T cells over a wide range of methylprednisolone doses. This pharmacodynamic model allows flexibility for characterizing any type of steroid dosing regimen and is relevant in describing complex response data for corticosteroid immunosuppressive effects in man.
Fisher
L E
LE
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo.
Ludwig
E A
EA
Jusko
W J
WJ
D002940:Circadian Rhythm / Q000187:drug effects*; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008954:Models, Biological; D015233:Models, Statistical; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology
D008775:Methylprednisolone