Pilot study of zonisamide (1,2-benzisoxazole-3-methanesulfonamide) in patients with refractory partial seizures

A new anticonvulsant compound, zonisamide (1,2 benzisoxazole-methanesulfonamide), was studied in 10 adults with medically refractory partial seizures. Following a single oral dose of 400 mg, peak plasma levels occurred an average of 2.8 h after dosing, and the mean clearance from plasma was 2.34 L/h. Whole blood concentrations were higher than plasma concentrations because of red blood cell binding. Steady-state plasma concentrations were higher than predicted from a linear kinetic model. In most patients, seizure frequency was reduced after zonisamide was substituted for a standard antiepileptic drug. Dose-related reversible side effects in the central nervous and gastrointestinal systems were observed. Most patients tolerated doses between 5.2 and 12.5 mg/kg/day.