Steady-state pharmacokinetics of zonisamide, an antiepileptic agent for treatment of refractory complex partial seizures

A 56-day pharmacokinetic study of zonisamide was conducted in 24 healthy volunteers. Steady state was achieved in 29 days including two dose escalations, and in an average of 15 days from the last dose adjustment. Twice-daily administration of 200 mg every 12 hours produced a 14% serum level fluctuation at steady state. After once-daily administration of 400 mg, a 27% serum level fluctuation was observed. The terminal-phase half-life after the last dose was 63 to 69 hours, which is consistent with the half-life of 52 to 60 hours found in single-dose studies. This result demonstrates that zonisamide is not an autoinducer. Serum oral clearance of 0.60 to 0.71 L/hr (0.121-0.132 mL/min/kg) was similar to that observed in other multiple-dose studies.