Comparison of valproate concentrations in human plasma, CSF and brain tissue after administration of different formulations of valproate or valpromide.

The concentration of valproate was measured in plasma, CSF and brain tissue of patients who underwent resective surgical treatment because of severe temporal lobe epilepsy after pretreatment with either a sustained release formulation of valproate (Depakine Chrono; 5 patients), the conventional formulation of valproate (Depakine; 6 patients) or valpromide (Depamide; 2 patients). With a mean serum value for all 13 patients of 32.3 micrograms/g valproate, the mean brain/serum ratio was 15.1% (SD 6.1%). The valproate concentration of the hippocampus was significantly higher than that of the amygdala and patients who had the sustained release formulation had significantly higher valproate concentration in the CSF and in the hippocampal formation than those patients who had the conventional valproate. Since a few patients had tumors, whereas others had varying degrees of gliosis, it cannot be ruled out that these differences are the result of different histopathological conditions with related differences in blood-brain barrier functions.