Effects of sodium valproate on diazepam: kinetic profiles in plasma, erythrocytes, and different brain areas in the rat.

The kinetic profiles of diazepam (DZP) were investigated in plasma, erythrocytes, and discrete brain areas in the rat, and the effects of valproic acid (VPA), given as sodium valproate, on kinetic parameters were analyzed. The experiments were performed on two groups of rats treated daily for 15 days, the first receiving only DZP (5 mg/kg/day i.m.), the second treated with DZP (5 mg/kg/day i.m.) and VPA (200 mg/kg/day i.p.). Our results indicate that VPA influences the plasma-protein binding and erythrocyte levels of DZP, as well as its kinetic profile. These data are discussed with regard to the modifications observed in the different brain areas (cerebellum, hippocampus, whole cortex, and pons-medulla) during administration of VPA and DZP. The results presented in this study offer evidence that VPA exerts a peculiar action on the "impregnation" and kinetics of DZP in the CNS, and therefore these findings may be of importance in clinical pharmacology and treatment of epilepsies.