Carbamazepine and carbamazepine-10,11-epoxide serum concentrations in epileptic children

Carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-epox) steady-state serum concentrations were measured in 82 children who had generalized tonic-clonic, or partial seizures. There was no correlation between a given dose and serum concentrations, whether other anticonvulsant drugs were used or not. Epileptic children receiving polytherapy (CBZ associated with one or more of the following drugs: phenobarbital, primidone, phenytoin, ethosuximide) had significantly different CBZ clearance values and percent CBZ-epox than did patients given CBZ alone. Even though given lower doses, girls had higher CBZ concentrations and lower CBZ clearance values than did boys. Older girls had lower serum concentrations of CBZ-epox than did younger girls. Seizure-free children had higher CBZ serum levels and lower CBZ clearance values than did those with uncontrolled seizures. The percentage of CBZ-epox in children with uncontrolled seizures was significantly higher than in children without seizures. These data indicate that serum levels of CBZ and CBZ-epox correlate more with factors such as associated drugs, age, and sex than with administered dose. Therefore, CBZ serum level monitoring represents an essential means of individualization of anticonvulsant drug therapy.