Postmortem Concentrations of Phenytoin in Different Regions of the Brain and in the Serum

Postmortem concentrations of phenytoin (PHT) were determined by high-performance liquid chromatography in the serum (total and free) and in specified areas of the brain (frontal, temporal, occipital cortex and white matter, as well as cerebellum) of 18 epileptic patients who died following chronic diseases (group A) and of six otherwise healthy epileptic patients who died suddenly and unexpectedly (group B). The free concentrations in the serum correlated considerably better (r = 0.987) than the total concentrations in the serum (r = 0.871) with the concentrations in the frontal cortex. The concentrations in the frontal cortex were about nine times that of the free serum concentrations. The data show that the PHT concentrations in the frontal, temporal and occipital cortex largely agree. The concentrations in the white matter were significantly higher (frontal region 54%, temporal region 30%, occipital region 36%) than in the cortex. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical with those in the frontal cortex. Regression analysis showed that on comparable total serum concentration the patients of group A had significantly higher free serum concentrations and significantly higher concentrations in the frontal cortex than the patients of group B. In respect of the concentration ratios cortex to serum free and in regard of the local distribution of PHT in the brain no difference, however, was found between those patients who died from chronic diseases and those who died suddenly. This means that the various diseases and organ failures which resulted in the death of the patients influenced neither the passage of PHT from the serum (free) to the brain, nor the local distribution of PHT in the brain. Our data do not support the supposition that therapy resistance or damage of the cerebellar cortex in spite of therapeutic serum concentrations are explainable by individually or locally varying concentrations in the brain.