LACK OF INFLUENCE OF HISTOPATHOLOGICAL CHANGES ON CARBAMAZEPINE AND CARBAMAZEPINE-10,11-EPOXIDE CONCENTRATIONS IN THE BRAIN CORTEX OF EPILEPTIC PATIENTS

Post-mortem concentrations of carbamazepine (CBZ) and its anticonvulsi ve metabolite carbamazepine-10,11-epoxide (CE) were determined in diff erent lesions of the cerebral cortex and in the serum (total and free) from 13 epileptic patients. Twenty cortical specimens were obtained f rom the superior frontal gyrus, the temporopolar region and the neocer ebellum. The cortical samples showed various pathological changes char acterized by augmented glial cells, fibre gliosis or ulegyria as well as abundant corpora amylacea or encephalitic signs of viral type besid es neuronal depletion. The CBZ and CE concentrations in the 20 conical lesions were not significantly decreased when compared to the control specimens of 32 epileptic patients without essential histopathologica l alterations of the specified cortical areas (p < 0.05). A comparable result had been found in our former study on phenytoin (PHT) and phen obarbital (PB). Six patients with cortical lesions of the present seri es had already been included in this PHT/PB study. Five of these patie nts revealed unchanged CBZ and CE as well as PHT and PB concentrations . Only in one neocerebellar specimen the CE concentration was just abo ve the upper 95% confidence limit of the control group. But, most prob ably this finding has no further relevance. The results greatly favour the nonspecific binding of CBZ and CE to cerebral tissue constituents .