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.

BackgroundLevetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in managing SE and CS.HypothesisLevetiracetam is rapidly absorbed after rectal administration in dogs and maintains target serum concentrations for at least 9 hours.AnimalsSix healthy privately owned dogs between 2 and 6 years of age and weighing 10–20 kg.MethodsLevetiracetam (40 mg/kg) was administered rectally and blood samples were obtained immediately before (time zero) and at 10, 20, 40, 60, 90, 180, 360, and 540 minutes after drug administration. Dogs were observed for signs of adverse effects over a 24‐hour period after drug administration.Results C LEV at 10 minutes was 15.3 ± 5.5 μg/mL (mean, SD) with concentrations in the target range (5–40 μg/mL) for all dogs throughout the sampling period. C max (36.0 ± 10.7 μg/mL) and T max (103 ± 31 minutes) values were calculated and 2 disparate groups were appreciated. Dogs with feces in the rectum at the time of drug administration had lower mean C max values (26.7 ± 3.4 μg/mL) compared with those without (45.2 ± 4.4 μg/mL). Mild sedation was observed between 60 and 90 minutes without other adverse effects noted.Conclusions and Clinical ImportanceThis study supports the use of rectally administered levetiracetam in future studies of clinical effectiveness in the management of epileptic dogs.