Pharmacokinetic and Dose Tolerability Study of ADD 94057 in Comedicated Patients with Partial Seizures

Summary: ADD 94057, a metabolite of fluzinamide, manufactured by the A. H. Robins Company, blocks chemically‐ and electrically‐induced seizures in animals. The primary objective of this open add‐on study was to evaluate patient tolerability of ADD 94057 at ascending target plasma concentrations. Nine subjects with medically refractory seizures were receiving phenytoin (PHT, 3), carbamazepine (CBZ, 3), or both (3). A pharmacokinetic profile after a single oral 400‐mg dose of ADD 94057 was used to calculate ADD 94057 dosages. After a 4‐week baseline period, patients were treated for 4 weeks with weekly ADD 94057 dosage escalations. Two patients completed the study at their assigned highest dosage level; the other patients finished the study at lower dosages. The patients receiving PHT (but not CBZ) tolerated higher plasma concentrations of ADD 94057 than did patients receiving CBZ, alone or in combination with PHT. Adverse experiences included headache, ataxia, blurred vision, diplopia, dizziness, lightheadedness, and mild confusion. Eight of nine patients had reductions in seizure frequency from baseline.