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Denzimol, a new anticonvulsant drug, is currently undergoing clinical evaluation. In this paper we report its use in six patients who were also taking carbamazepine and two patients taking phenytoin. There was a striking elevation of serum carbamazepine, carbamazepine-10, 11 epoxide and phenytoin concentrations in all patients on the addition of denzimol therapy. The interaction with carbamazepine is greater in severity than any other reported to date and denzimol's interaction with both carbamazepine and phenytoin is likely to prove of major clinical significance.

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sodium valproate, with a correlation between plasma CBZ-10,11-EPOX and side-effects when either drug was introduced or withdrawn, the plasma levels of CBZ itself and of sodium valproate being within the 'therapeutic range'.

A method of measuring carbamazepine-10,11-epoxide (CBZ-10,11-EPOX) has been developed and used to monitor plasma concentrations in children suffering from various forms of epilepsy. Children stabilised on standard doses of CBZ alone showed a ratio of CBZ-10,11-EPOX/CBZ of 18.92 +/- 8.08, expressed as a percentage of the CBZ concentration, while those on multiple-drug therapy (with the exception of benzodiazepines and phenobarbitone) showed both increased values of CBZ-10,11-EPOX/CBZ ratio and increased absolute concentrations of CBZ-10,11-EPOX in plasma. These changes correlated with clinical side-effects which could not be attributed to CBZ itself or to the other drugs administered concurrently.