title: Zonisamide: pharmacokinetics, efficacy, and adverse events in children with epilepsy.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neuropediatrics, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Wallander
authors.affiliation: Department of Internal Medicine, Center for Pharmacoepidemiology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Ohman
authors.affiliation: Department of Neuropediatrics, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Dahlin
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007555:Isoxazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D008297:Male; D008657:Metabolic Clearance Rate; D012189:Retrospective Studies; D012737:Sex Factors; D016896:Treatment Outcome; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D000078305:Zonisamide