Correlation between plasma carbamazepine-10,11-epoxide concentration and drug side-effects in children with epilepsy

Ninety children with epilepsy were treated with carbamazepine (CBZ) alone or with other anticonvulsant drugs. Side-effects were noted in 14 patients. When 25 patients treated with CBZ alone (group 1) were compared with 27 on CBZ and sodium valproate (group 2) and with 38 on CBZ and one or more other anticonvulsants (group 3), the incidence of side-effects was two in group 1 (of whom one patient had a toxic plasma level of CBZ), but 12 in groups 2 and 3 combined. In all but three of the 14 patients with side-effects, plasma levels of CBZ were within the 'therapeutic range'. A significant difference was found between the carbamazepine-10,11-epoxide (CBZ-10,11-EPOX) levels in plasma and CBZ-10,11-EPOX/CBZ ratio in patients with and without side-effects. For five patients on CBZ and other drugs, changes in treatment resulted in changes in side-effects, and also in CBZ-10,11-EPOX levels. Three of these patients showed an interaction between CBZ and sodium valproate, with a correlation between plasma CBZ-10,11-EPOX and side-effects when either drug was introduced or withdrawn, the plasma levels of CBZ itself and of sodium valproate being within the 'therapeutic range'.