Abstract
The clinical effects and plasma levels of zonisamide (ZNS) were investigated in children with cryptogenic localization-related epilepsies, who were administered ZNS once a day as a single drug. ZNS is absorbed slowly from the gastrointestinal tract, and its biological half-life is long compared with the other prevalent antiepileptic drugs.
The patients comprised 45 previously untreated children aged 3 months to 14 years (mean, 8 years and 6 months) with any of simple, complex or secondarily generalized partial seizures. A daily dose of 2mg/kg of ZNS was introduced and the dosage was increased gradually to the initial maintenance daily dose of 8mg/kg. ZNS was prescribed once a day in the morning. Blood samples for determination of the plasma levels were taken before and 4 hours after the morning dose, each of which represents the trough and peak levels in a day.
The initial maintenance daily dosage of ZNS (8.01±0.54mg/kg) gave the trough and peak plasma levels of 27.1±8.2 and 33.4±9.1μg/ml, respectively. The peak totrough plasma level ratios were as small as 1.25±0.13. The plasma level (μg/ml) to dose (mg/kg/day) ratios estimated by the trough and peak plasma levels increased both with the advance in age, but the peak to trough plasma level ratios were maintained almost uniformly throughout the pediatric age period.
Of the total 25 patients who were followed up clinically for more than 12 months, seizures were not controlled in 5 with the initial maintenance dosage. Three of the 5 patients who had seizure recurrences showed the trough plasma ZNS levels around 15μg/ml. In 3 patients whose peak levels were above 40μg/ml, the dosage was decreased to tolerable levels because of the continuous complaint of drowsiness.However, for the period of treatment, ranging from 12 to 34 months (mean, 15.7months) from starting ZNS therapy, complete seizure control was obtained in 17 out of the 25 patients on the initial maintenance dosage.
Once-daily dose of ZNS monotherapy assisted by blood level monitoring may be effective for the control of partial seizures in children.
