Zonisamide overview of the United States experience

Abstract

Although established antiepilepsy drugs (AEDs) are efficacious and new drugs have become available to treat patients with epilepsy, at least 30% of all patients remain refractory to available treatment.1 Continued efforts to identify and develop new compounds for the treatment of epilepsy motivate all concerned because of the plight of so many patients. In the following sections, data are provided that document the US experience in the development and ultimate availability of zonisamide for treatment of patients with partial seizures. Development of zonisamide in the United States began in 1982 as a collaborative project between Dainippon Pharmaceuticals Co, and Parke–Davis. Pilot studies of bioavailability and pharmacokinetics involved about 270 healthy volunteers and also patients with epilepsy. Both open and controlled protocols that were performed in the mid-1980s suggested that zonisamide had efficacy for treatment of patients with refractory partial seizures.2,3 However, drug development in the United States was halted when 3.7% of patients enrolled in studies developed renal calculi. Since studies in Europe and Japan showed both efficacy and safety4,5 with lower rates of calculi formation, studies in the US were resumed in the 1990s. As detailed in the following reports, bioavailability and bioequivalence were evaluated in five studies of 72 patients and healthy volunteers aged 19–69 years. Fourteen studies of 172 patients and healthy volunteers aged 18–71 years reported the effects of