Phenobarbital treatment of status epilepticus in a rodent model

Abstract

Although phenobarbital is frequently used in the treatment of status epilepticus, little has been published concerning the dose or serum concentration which effectively control adult status. We studied the efficacy of phenobarbital in controlling status in a rat model which induces generalized tonic-clonic seizures (GTCS) which respond to other drugs at serum concentrations similar to those reported to be effective in human status. We found that phenobarbital is rapidly absorbed following intraperitoneal injection, but entry into brain is delayed. Brain entry was facilitated during uncontrolled status epilepticus. The ED50 values for control of seizures in this model rose in a dose-dependent manner for increasing levels of seizure control, from 14.2 mg/kg for control of GTCS to 76.6 mg/kg for control of all motor and electrographic ictal activity. Raising serum concentrations above the 20 micrograms/ml required to control GTCS produced increasingly better control of the various types of ictal activity seen in this model.