Pharmacokinetic-pharmacodynamic modeling of prednisolone-induced lymphocytopenia in man.

The lymphocytopenic effect of prednisolone as quantified by OKT3- and OKT4-positive lymphocyte counts in peripheral blood was studied. Single oral prednisolone doses of 10, 30 and 60 mg, respectively, were given to three groups of five subjects. The time courses of prednisolone concentration and lymphocytopenic effects were related by a pharmacokinetic-pharmacodynamic model. The computer program NONLIN was used for parameter estimation. The pharmacodynamic component of the model was a hyperbolic function in which a threshold concentration parameter had to be incorporated. Apparently, this parameter represents depletion of endogenous hydrocortisone after the administration of prednisolone. The results of this study suggest that the prednisolone-induced lymphocytopenia is not related to mRNA transcription and protein synthesis. Furthermore, prednisolone and hydrocortisone seem to be equipotent in man with respect to the studied effect. Smaller doses of prednisolone are relatively more effective due to saturation of the effect and increasing depletion of endogenous hydrocortisone by higher doses.