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Although glucocorticoid therapy is essential for the treatment of severe inflammatory disorders, there is no systematic approach to patient variables that may affect availability of a steroid dose. After the development of a data base of pharmacokinetic parameters, we examined glucocorticoid pharmacokinetics in 54 patients between 2 and 70 years of age using 70 pharmacokinetic studies after administration of intravenous methylprednisolone (n = 25), oral methylprednisolone (n = 15), intravenous prednisolone (n = 18), and oral prednisone (n = 12). Eleven patients had unusually rapid methylprednisolone elimination (clearance, 565 to 837 ml/min/1.73 m2; population mean, [+/- SD] 380 +/- 100 ml/min/1.73 m2) without an identifiable cause. Incomplete absorption of methylprednisolone and prednisone was observed in three patients and one patient, respectively. Evaluation of glucocorticoid pharmacokinetics in children aged 1 year 8 months to 18 years demonstrated a significant inverse correlation (r = 0.88; p less than 0.001) between prednisolone clearance and age. It is therefore important to consider age in the interpretation of pharmacokinetic data. To simplify measurement of prednisolone clearance, a single-dose single-point method was developed. This was based on a highly significant relationship between the 6-hour postdose prednisolone concentration and prednisolone clearance (log prednisolone clearance = 2.66 + [6-hour postdose concentration] [-0.00167]; r2 = 0.96; p less than 0.0001). Evaluation of glucocorticoid pharmacokinetics in the clinical setting can be used to identify abnormalities in absorption, elimination, and patient compliance. This technique can be used to individualize glucocorticoid dosing regimens.

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Prednisolone and methylprednisolone pharmacokinetic parameters were evaluated in asthmatic children receiving concomitant anticonvulsant therapy. On separate study days, 15 children receiving either phenobarbital, carbamazepine, phenytoin, or combination anticonvulsant therapy were administered an intravenous dose of prednisolone or methylprednisolone and compared with a pediatric population not receiving anticonvulsant therapy. Plasma clearance of prednisolone in subjects receiving phenobarbital, carbamazepine, and phenytoin and in control subjects was 302.7 +/- 74.6, 383.2 +/- 53.8, 378.9 +/- 50.7, and 214.0 +/- 28.8 ml/min/1.73 m2 (mean +/- 1 SD), whereas plasma clearance of methylprednisolone was 1179.1 +/- 519.4, 1687.0 +/- 109.9, 2209.5 +/- 473.8, and 381.7 +/- 98.4 ml/min/1.73 m2, respectively. Bioavailability of prednisolone after the oral administration of prednisone and methylprednisolone ranged from 86% to 104% during anticonvulsant therapy. Three individuals reevaluated 13 to 20 days after discontinuing anticonvulsant therapy demonstrated pharmacokinetic parameters similar to those of the control group. Limited studies performed in patients receiving combination anticonvulsant therapy did not demonstrate an additive effect on prednisolone elimination. Differences in the degree of enhancement of prednisolone and methylprednisolone disposition in all three anticonvulsant study groups suggest that different metabolic pathways may be involved.