Valproate increases diazepam impregnation selectively in CNS of the rat after subchronic administration

Valproate-Diazepam association is not unusual in the treatment of epilepsies. The present paper investigates in an experimental study the effect of sodium valproate (VPA) on the regional cerebral level of diazepam (DZP), and the relationship with plasma or erythrocytes amounts after subchronic administration. The VPA addition increases the DZP levels in peripheral and central compartments. The results shows a linear correlation between the drug concentration in all areas studied and the plasmatic or erythrocytic amounts during the CNS-impregnation phase. The VPA influence is greater in the CNS where the DZP impregnation is selectively increased, specially in cortex and cerebellum.