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.