Receptor-based pharmacokinetic-pharmacodynamic analysis of corticosteroids.

The pharmacodynamics of three corticosteroids were investigated after intravenous administration of the phosphate esters of methylprednisolone, dexamethasone, and triamcinolone acetonide to healthy subjects at 20, 50, and 80 mg as well as placebo. Twenty-two different pharmacodynamic parameters were followed as a function of time for 48 hours. Statistically significant effects of the glucocorticoids were an increase in blood glucose levels, a decrease in the number of lymphocytes, eosinophils, basophils, and monocytes, and an increase in the number of granulocytes and stab cells. For the most significant pharmacodynamic effects (lymphocytes, granulocytes, and glucose) a previously derived integrated pharmacokinetic/pharmacodynamic model using plasma concentrations, protein-binding data, and in vitro receptor-binding affinities was used to predict the pharmacodynamic effect-time profiles. Good agreement of predicted and measured effects was observed, confirming the validity of the model. The clinical significance of the model was demonstrated by comparison of model-predicted maintenance doses with empirically determined clinical equivalency doses.

RCT Entities:   Population Interventions Outcomes