Receptor‐Based Pharmacokinetic‐Pharmacodynamic Analysis of Corticosteroids

Abstract

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.

Multicenter Study of Voriconazole Pharmacokinetics and Therapeutic Drug Monitoring

“…Differences in the degrees of interaction observed with different glucocorticoids are also apparent. In both the multiple regression and univariate analysis (Tables 3 and 4), coadministration of dexamethasone and methylprednisolone reduced voriconazole concentrations to a greater extent than prednisone or prednisolone; these results correlate with the higher glucocorticoid receptor potency observed with dexamethasone and methylprednisolone (9).…”

Impact of glucocorticoids on insulin resistance in the critically ill

“…The perpatient median steroid dose was equivalent to 200mg/d of hydrocortisone [14][15][16]. Patients were excluded if they received β-blockers or ACE-inhibitors, as these therapeutics can affect glucose metabolism and insulin sensitivity in an opposing fashion [17][18][19].…”

Is Dexamethasone an Effective Alternative to Oral Prednisone in the Treatment of Pediatric Asthma Exacerbations?

“…17 It has a 36-to 72-hour half-life, compared with the 12-to 36-hour half-life of prednisone, and therefore requires fewer doses. [18][19][20] Furthermore, dexamethasone tastes better 11 and costs less in terms of unscheduled revisits. 21 Cross et al 22 published a brief over view of the literature examining the use of singledose dexamethasone for pedi atric asthma exacerbations in ambulatory care settings.…”