Related Experiment Videos
Prednisolone and methylprednisolone kinetics in children receiving anticonvulsant therapy
M Bartoszek1, A M Brenner, S J Szefler
1Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Insights
Asthmatic children on anticonvulsants show altered prednisolone and methylprednisolone pharmacokinetics. Stopping anticonvulsant therapy normalized these drug parameters in a small subset of patients.
Area of Science:
- Pharmacology
- Pediatric Asthma Management
- Drug Interactions
Background:
- Asthmatic children often require corticosteroids like prednisolone and methylprednisolone.
- Concomitant use of anticonvulsant therapy can potentially alter drug metabolism.
- Limited data exists on the pharmacokinetic impact of anticonvulsants on pediatric corticosteroid use.
Purpose of the Study:
- To evaluate the pharmacokinetic parameters of prednisolone and methylprednisolone in asthmatic children receiving anticonvulsant therapy.
- To compare these parameters with those of pediatric patients not on anticonvulsants.
- To investigate potential alterations in drug clearance and bioavailability.
Main Methods:
- A study involving 15 asthmatic children on phenobarbital, carbamazepine, phenytoin, or combination anticonvulsants.
- Intravenous administration of prednisolone or methylprednisolone on separate days.
- Comparison with a control pediatric group not receiving anticonvulsant therapy.
- Oral bioavailability assessment of prednisone and methylprednisolone.
Main Results:
- Plasma clearance of both prednisolone and methylprednisolone was significantly increased in children receiving anticonvulsant therapy compared to controls.
- Oral bioavailability of prednisolone and methylprednisolone remained within normal ranges (86%-104%) during anticonvulsant use.
- Pharmacokinetic parameters returned to baseline levels in three subjects after discontinuing anticonvulsant medication.
Conclusions:
- Concomitant anticonvulsant therapy significantly enhances the disposition of prednisolone and methylprednisolone in asthmatic children.
- The observed differences suggest that various anticonvulsants may influence corticosteroid metabolism through distinct pathways.
- Discontinuation of anticonvulsants can reverse these pharmacokinetic changes.
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.