Abstract
Background Zonisamide is a new generation antiepileptic drug (AED) widely used in children with
refractory epilepsy, although until recently, it was used to a large extent as off-label
or unlicensed medication due to the lack of evidence-based studies. Children have
a different pharmacokinetic profile than adults and an adult dose regimen cannot be
directly translated into pediatric use.
Patients and Methods In this retrospective noninterventional study of the medical records of 75 children
with pharmacoresistant epilepsy, the pharmacokinetics, efficacy and safety of zonisamide
were examined. The dose-to-concentration ratio, the daily weight-normalized dose of
zonisamide divided by its plasma concentration, was used as a measure of clearance.
In addition, data on the efficacy of zonisamide to reduce seizures and reported adverse
events were extracted from the medical records and analyzed.
Results Young children (range, 0–4 years) had a significantly increased zonisamide clearance
compared with older ones (range, 5–17 years) and those with enzyme-inducing comedication
(carbamazepine, phenobarbital, or phenytoin) had increased clearance compared with
those on nonenzyme inducers; the increases were 1.7-fold and 1.8-fold, respectively.
No significant difference in clearance was found between female and male subjects.
The clearances of concomitant AEDs were not affected by zonisamide administration.
The overall efficacy of zonisamide for reducing seizure frequency ≥50% was 35% and
the most frequent adverse event was fatigue, reported in 23% of the patients.
Conclusion Patients with enzyme-inducing comedication or of young age (range, 0–4 years) might
need higher weight-normalized doses to achieve the same plasma levels as in patients
with no enzyme-inducing comedication or patients of older age. Zonisamide was not
found to influence the pharmacokinetics of concomitant AEDs. The shortage of pharmacokinetic
studies of zonisamide in children highlights the need for research of this kind.
Keywords
zonisamide - pharmacokinetics - children - age - comedication
