The effect of clobazam on steady state plasma concentrations of carbamazepine and its metabolites.

Steady state metabolite/parent drug plasma ratios were measured in 15 epileptic patients on carbamazepine (CBZ) monotherapy and in seven patients treated with CBZ and clobazam (CLB). CBZ plasma concentrations did not differ between the two groups but patients also treated with CLB exhibited higher concentrations of CBZ-10,11-epoxide (CBZ-E) and trans-10,11-dihydro-10,11-dihydroxy-CBZ (CBZ-T). Ratios between all of the metabolites of CBZ and the parent compound were higher in patients on polytherapy but the ratio between metabolites was not different. CLB comedication causes a moderate increase (about 1.5-fold) in CBZ metabolism, probably by inducing its epoxidation.