Effect of denzimol on carbamazepine and carbamazepine-10,11-epoxide concentrations in serum, liver, spleen and different brain regions of the rat: an inhibitory metabolic interaction

The effect of denzimol (DNZ) on the disposition of carbamazepine (CBZ) and its primary metabolite carbamazepine-10,11-epoxide (CBZ-E) in serum, liver, spleen and seven brain regions of the rat was assessed. Coadministration with DNZ for 5 or 10 days resulted in an increase in CBZ and a decrease in CBZ-E concentrations in serum, liver and spleen, consistent with a metabolic (hepatic cytochrome P450 mono-oxygenases) inhibitory interaction. After 15 days of co-administration the concentration of CBZ-E was also increased in these tissues, suggestive of epoxide hydratase inhibition in addition. The magnitude of these concentration changes was much greater in the brain indicating that the total serum concentration of CBZ or CBZ-E may not be a reliable index of the neuropharmacological severity of CBZ-DNZ interaction.