Contribution of carbamazepine-10-11-epoxide to neurotoxicity in epileptic children on polytherapy

Carbamazepine-10-11-epoxide [CBZ-E] is a major metabolite of car bamazepine [CBZ]. CBZ-E has received recent attention because of its possible adverse side effects. A CBZ-E plasma level above 9 uM/L has been reported to be more often associated with side effects than are lower levels. We retrospectively reviewed health records of 88 children aged 6-16 years [mean, 10.7 years] on CBZ therapy. CBZ-E and other antiepileptic drug plasma levels were measured at the time of their neurologic evaluation. Three groups of patients were identified; a monotherapy group [n=48], a polytherapy group without neurotoxicity [n=36], and a polytherapy group with neurotoxicity [n=4]. All neurotoxic patients were on polytherapy and had plasma levels of CBZ and other AEDs within the therapeutic range but their plasma CBZ-E values were high [mean=15.8 microM/L, range 11-23]. CBZ-E plasma levels of the polytherapy group [11.6 microM/L] were significantly higher than those of the monotherapy group [5.8 micro M/L; p<0.001]. Monitoring CBZ-E plasma levels may provide more information on adverse effects of CBZ in children on polytherapy, although CBZ-E alone doesn't account for neurotoxicity