Postmortem concentrations of phenobarbital, carbamazepine, and its metabolite carbamazepine-10,11-epoxide in different regions of the brain and in the serum: analysis of autoptic specimens from 51 epileptic patients.
Postmortem concentrations of phenobarbital (PB), carbamazepine (CBZ), and its metabolite carbamazepine-10,11-epoxide (CE) 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 51 deceased epileptic patients. The concentrations of PB and CBZ in the frontal cortex were approximately 1.4 times higher, and of CE were 1.1 times higher than the total concentrations in the serum. Furthermore, the concentrations of PB in the frontal cortex were approximately 2.1 times, of CBZ were 4.5 times, and of CE were 2.1 times higher than the free concentrations in the serum. The distribution of the three substances in the brain is rather homogeneous and seems to follow basic physicochemical principles. This means that the concentrations of the substances in the white matter are, depending on their lipophilicity, modestly but significantly higher than in the cortex. Small and in part statistically significant concentration differences between different regions of the cortex and also of the white matter may be explained by differences in the lipid content of the respective regions and by the lipophilicity of the respective substance. The concentrations in the cerebellar hemisphere (neocerebellum) were nearly identical to those in the frontal cortex. Remarkably increased or decreased concentrations were not observed in any region of the brain.
Rambeck
B
B
Department of Biochemistry, Gesellschaft für Epilepsieforschung e. V., Bethel, Bielefeld, Germany.
Schnabel
R
R
May
T
T
Jürgens
U
U
Villagran
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D001923:Brain Chemistry; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000032:analysis* / Q000097:blood; D014018:Tissue Distribution
D002220:Carbamazepine; C012227:carbamazepine epoxide; D010634:Phenobarbital