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 anticonvulsive metabolite carbamazepine-10,11-epoxide (CE) were determined in different lesions of the cerebral cortex and in the serum (total and free) from 13 epileptic patients. Twenty cortical specimens were obtained from the superior frontal gyrus, the temporopolar region and the neocerebellum. The cortical samples showed various pathological changes characterized by augmented glial cells, fibre gliosis or ulegyria as well as abundant corpora amylacea or encephalitic signs of viral type besides neuronal depletion. The CBZ and CE concentrations in the 20 cortical lesions were not significantly decreased when compared to the control specimens of 32 epileptic patients without essential histopathological alterations of the specified cortical areas (p < 0.05). A comparable result had been found in our former study on phenytoin (PHT) and phenobarbital (PB). Six patients with cortical lesions of the present series had already been included in this PHT/PB study. Five of these patients revealed unchanged CBZ and CE as well as PHT and PB concentrations. Only in one neocerebellar specimen the CE concentration was just above the upper 95% confidence limit of the control group. But, most probably this finding has no further relevance. The results greatly favour the nonspecific binding of CBZ and CE to cerebral tissue constituents.
Schnabel
R
R
Institute of Neuropathology, Ludwig Maximilians-University, München, Germany.
Rambeck
B
B
May
T
T
Jürgens
U
U
Lahl
R
R
Fritsch
W
W
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide