title: Zonisamide monotherapy with once-daily dosing in children with cryptogenic localization-related epilepsies: clinical effects and pharmacokinetic studies.
abstract: Clinical effects and pharmacokinetics of once-a-day pediatric zonisamide (ZNS) monotherapy were investigated in 72 children (range, 3 months to 15 years; mean age, 8 years and 3 months) with cryptogenic localization-related epilepsies with simple, complex, or secondarily generalized partial seizures; none had prior epilepsy treatment. ZNS was initiated at 2mg/kg; daily dosage was doubled at weekly intervals to achieve maintenance dosage (8.0 mg/kg; mean, 7.97 +/- 0.55 mg/kg). Blood samples determined trough and peak plasma levels; levels were 27.0 +/- 9.4 microg/ml and 33.8 +/- 10.8 microg/ml, respectively, with ratios as small as 1.28 +/- 0.15. Plasma level to dose ratios increased with age; peak-to-trough ratios were not age variable. Seizures were not controlled in 23 of 72 patients; low trough plasma levels (approximately 15 microg/ml) were observed. Drowsiness/short attention span in five patients instigated a dosage decrease (peak plasma levels >40 microg/ml). During treatment (6-43 months; mean, 27.2 months), seizure control occurred in 57 of 72 patients (79.2%), including eight refractory patients. In 12 patients with uncontrolled seizures and high ZNS levels, carbamazepine (CBZ) was added (BID; mean total dose, 15.1 +/- 3.0 mg/kg) to ZNS (QD; mean dose, 11.1 +/- 2.5 mg/kg); drug interactions were examined.
authors.affiliation: Saganihara Ryouikuen, Institute for Severe Disabled, 1-21-9 Wakamatsu Sagamihara, Kanagawa 229-0014, Japan. s-ryouikuen@tbd.t-com.ne.jp
authors.forename: Hisao
authors.initials: H
authors.lastname: Miura
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002220:Carbamazepine / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000145:classification / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007555:Isoxazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D016896:Treatment Outcome; D000078305:Zonisamide
chemical_list: D000927:Anticonvulsants; D007555:Isoxazoles; D002220:Carbamazepine; D000078305:Zonisamide