Age and antiepileptic drugs influence topiramate plasma levels in children

The influence of age and comedication on the dose-to-level ratio of topiramate was examined in 91 children with epilepsy treated with topiramate. The topiramate dosing and plasma concentrations, as well as those of their concomitant antiepileptic drugs were examined retrospectively. The dose-to-level ratio was used as a measure of clearance and was calculated as the weight-normalized topiramate dose (mg/kg/day) divided by the steady-state trough plasma drug level in the child. The children were classified in age groups and treatment groups; topiramate was administered with an enzyme inducer (n = 32), with a nonenzyme inducer (n = 49), or as monotherapy (n = 10). The topiramate clearance in children aged 0-8 years compared with those aged 9-17 years was more than twofold higher if treated with an enzyme-inducing antiepileptic drug and 1.5-fold higher if treated with a nonenzyme inducer. Children receiving enzyme inducers had a more than twofold higher clearance compared with those who did not. Within all age groups, significant differences in topiramate clearance were observed between those receiving enzyme inducers and those receiving nonenzyme inducers or monotherapy. Thus younger age and concomitant enzyme inducers, both acting independently, significantly increased the clearance of topiramate in children. This effect has to be considered to optimize treatment in the individual patient. (C) 2004 by Elsevier Inc. All rights reserved.