Abstract
A two-compartment dosed 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 leastsquares 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 AUCon 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 relevent in describing complex response data for corticosteroid immunosuppressive effects in man.
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Supported in part by grant GM 24211 from the National Institutes of General Medical Sciences, National Institutes of Health.
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Fisher, L.E., Ludwig, E.A. & Jusko, W.J. Pharmacoimmunodynamics of methylprednisolone: Trafficking of helper T lymphocytes. Journal of Pharmacokinetics and Biopharmaceutics 20, 319–331 (1992). https://doi.org/10.1007/BF01062461
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DOI: https://doi.org/10.1007/BF01062461