Relationship between ischemic damage and concentrations of phenytoin and phenobarbital in the brain cortex of epileptic patients in vegetative state at death.

Post-mortem concentrations of phenytoin (PHT) and phenobarbital (PB) were determined by high-performance liquid chromatography in the cortical matter of specified brain regions and in the serum (total and free) from 3 epileptic males in vegetative state and compared to the data of 45 deceased epileptic control patients. The duration of the vegetative state was 12 days, 15 days or about 4 months until death and was associated with corresponding stages of generalized ischemic brain damage. The histological examination was completed by immunohistochemical and morphometric methods. According to other investigators nerve cells are the major binding sites for PHT and PB in the cerebral cortex of rodents. But, in the 3 comatose patients the PHT and PB concentrations of the isocortex and neocerebellum were not significantly decreased in comparison with the control patients despite necrosis and loss of neurons as well as other distinct tissue alterations. The results strongly favor the non-specific binding of PHT and PB to cells and subcellular structures of the brain-mainly based on simple physico-chemical principles.