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R. Eugene Ramsay, MD; Edward J. Hammond, PhD; Robert J. Perchalski, MS; B. Joe Wilder, MD

Arch Neurol. 1979;36(9):535-539.

Abstract
• The optimal drug for the treatment of status epilepticus would be an effective anticonvulsant that rapidly enters the CNS, and remains concentrated in the tissue. Penetration of phenytoin, phenobarbital, and diazepam into the parenchyma of the cat brain was assessed after intravenous (IV) infusion. Maximum brain concentrations were reached at one minute (diazepam), three minutes (phenobarbital), and six minutes (phenytoin). Phenobarbital and phenytoin entered more slowly, but remained bound with similar brain concentrations at one minute and 60 minutes. Relatively free movement of diazepam in and out of the brain was found, with lower brain concentrations occurring 45 to 60 minutes after infusion. Peak phenytoin concentration occurred in the brain and CSF at the same time (six minutes), and constant plasma-CSF ratios were found after six minutes. The treatment of status epilepticus as indicated by the drug kinetics would be (1) initial use of IV diazepam to effect immediate seizure control due to more rapid penetration into the brain; and (2) subsequent rapid use of IV phenytoin or phenobarbital to maintain seizure control due to relative slow clearance of these drugs out of the brain, while diazepam has a quite rapid clearance.

Author Affiliations
From the Neurology Services, Veterans Administration Hospital and College of Medicine, University of Florida, Gainesville (Dr Hammond, Mr Perchalski, and Dr Wilder), and the Veterans Administration Hospital, Miami (Dr Ramsay).

Footnotes
Accepted for publication Oct 28, 1978.

Read before the Joint Meeting of the American Epilepsy Society and the American Electroencephalographic Society, Oct 1, 1977, Dearborn, Mich.

Reprint requests to Neurology Service (127), Veterans Administration Hospital, 1201NW 16th St, Miami, FL 33125 (Dr Ramsay).

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