Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy

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Abstract
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.

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