Zonisamide: The Arizona Experience

Abstract

Zonisamide (ZNS) is a new antiepileptic drug initially introduced in Europe, Japan and the United States (US) in the late 1980’s and was the first such drug to be clinically tested in the US, since the marketing of valproic acid in 1978. Reports of nephrolithiasis by European and US investigators resulted in the trials being terminated in the US during the open label phase. The present report is the result of a non-blind, historical controlled study of the safety and efficacy of zonisamide conducted at the University of Arizona as part of a nine-center US trial. Twenty patients, ten male and ten female, aged 18-54 were enrolled. Nineteen patients received zonisamide code named CI-912 at a dosage of 6.2-14 mg kg-1. Sixteen patients completed the study. Efficacy was defined as >50% reduction in seizures. Zonisamide was effective in reducing partial seizures with or without secondary generalization in 56.3% of patients who completed the study. No patient had significant alteration in CBC and SMA 16 requiring adjustment of dosage. The average plasma levels ranged from 10 to 31 µg mL-1 during treatment. The only major side effect that required discontinuation of treatment was the development of a skin rash in one patient. Two others discontinued the study due to personal reasons.