The therapeutic range for phenytoin - A reappraisal.

Serum levels of phenytoin were compared with seizure control in a prospective study of 31 patients with a wide variety of seizures of varying severity. Twenty-two patients were followed up for an average period of 15 months, and 9 for an average period of 6 months. Nine patients became seizure free (excellent control), and a greater than 50% reduction in seizure frequency occurred in 13 patients (good control). A less than 50% reduction in seizure frequency occurred in 9 patients (poor control). An excellent or good response was associated with mean levels within a therapeutic range in 9 patients, and with subtherapeutic levels in 13 patients. Only 2 patients with poor control reached mean levels within the therapeutic range. Even with frequent dose adjustments, it was impossible to achieve higher levels in this group. Patients with both mild, moderate, and severe seizures responded at levels which were both subtherapeutic and within the therapeutic range. Fluctuations of serum levels occurred in all patients, but was most marked in patients with a good response. The results show that the therapeutic range would not appear to be valid as patients responded to a wide range of levels irrespective of seizure severity.