Distribution of diphenylhydantoin in the brain during experimental status epilepticus of the cat.

The distribution of diphenylhydantoin (PHT) (40 mg/kg i.p.) in the brain was investigated in cats with convulsive generalized (group 1) and focal penicillin-induced status epilepticus (group 2), and in controls. A significant increase in the amount of PHT entering the brain during the convulsive status was found, with peak brain levels at 45 min (12 +/- 3.2 micrograms/g vs. 6.0 +/- 0.8 in normal cats, P less than 0.05). In the focal status brain concentrations of PHT reached levels intermediate between controls and group 1 cats. At 15 min, elevated blood levels of the drug were paralleled by increased concentrations in the brain, whereas at 30 and 45 min other factors, such as changes in cerebral blood flow, cerebral pH, vascular resistance, metabolic derangement and blood-brain barrier disruption were presumably responsible for the altered brain PHT uptake. The relevance of these data to clinical practice is discussed, in relation to the treatment of human status epilepticus and the potentially neurotoxic effects of the drug.