CARBAMAZEPINE AND ITS EPOXIDE - AN OPEN STUDY OF EFFICACY AND SIDE-EFFECTS AFTER CARBAMAZEPINE DOSE INCREMENT IN REFRACTORY PARTIAL EPILEPSY

We evaluated the efficacy, development of adverse effects, and possibl e correlation between the plasma concentration of carbamazepine (CBZ) and its major metabolite, carbamazepine-10,11-epoxide (CBZ-E), in a gr oup of epileptic patients in whom selective increases in CBZ doses wer e made, Eighteen patients with refractory partial epilepsy participate d in an open trial, Five were on monotherapy and 13 on polytherapy. Al l the patients were on CBZ before the trial and had plasma levels with in the therapeutic range (17-42 mu mol/L). After a baseline period, CB Z doses were progressively increased either to reach a 50% reduction i n seizure frequency for 2 months or until side effects appeared. Thirt y-nine percent of the patients had a 50% decline in seizure frequency, but only 17% improved for >6 months, Mild or moderate side effects we re observed in 78% of the patients. Side effects were correlated with CBZ plasma levels but not with CBZ-E plasma levels. Correlation betwee n CBZ and CBZ-E plasma levels were found in the monotherapy group, but not in the polytherapy group. Our results confirm that higher doses o f CBZ can successfully be used in some patients with refractory partia l epilepsy. Furthermore, the plasma level of CBZ-E does not seem to be a useful indicator of toxicity in CBZ-treated ambulatory epileptic pa tients.