Efficacy of intravenous phenytoin in the treatment of status epilepticus: Kinetics of central nervous system penetration

Abstract

Abstract Intravenous phenytoin (mean dose, 13.0 mg per kilogram of body weight) was administered to 14 patients at a rate not exceeding 100 mg per minute. Twelve hours after infusion the mean plasma phenytoin concentration was 10.2 μg per milliliter, and a therapeutic plasma concentration was found in 9 of the 14 patients. In 3 additional patients, during removal of a primary brain tumor, cortical samples were obtained after intravenous infusion of phenytoin (mean dose, 9.2 mg/kg). Rapid penetration of the brain was found. Concentrations at the end of infusion (16 μg/gm) and 60 minutes after infusion (23 μ/gm) were not significantly different. Six other patients received intravenous phenytoin (mean dose, 10.9 mg/kg) during pneumoencephalography. The cerebrospinal fluid phenytoin concentration gradually increased over 50 minutes. The plasma/cerebrospinal fluid ratio at 50 minutes was 11.0, which is approximately the ratio of total/free phenytoin in the plasma. An additional 10 patients in generalized convulsive status epilepticus were treated with intravenous phenytoin (mean dose, 12.2 mg/kg); status was controlled in 9 within 30 minutes. No major side‐effects were noted. Intravenous phenytoin rapidly enters the central nervous system and results in prompt and effective treatment of status epilepticus without suppressing higher cortical function or cardiorespiratory centers.