THE METABOLIZATION OF CARBAMAZEPINE TO CBZ-10,11-EPOXIDE IN CHILDREN FROM THE NEWBORN AGE TO ADOLESCENCE

CBZ-10,11-epoxide is a major metabolite of CBZ. It has anticonvulsive properties and may be respon sible for side-effects of CBZ treatment. Fifty-two children between the age of 2 weeks and 15 years were treate d with CBZ (mean dosage 17 mg/kg body weight) either as mono- (n = 36) or in polytherapy (n = 16). The drug was delivered as an oral solutio n, as a nonretarded tablet or, most frequently, as a retarded tablet. The duration of treatment ranged from 1 to 94 months with 23 patients being on treatment for less than 3 months. Blood samples were taken wi th random timing after the last ingestion of the drug. The relative co ncentration of CBZ epoxide (expressed in % of CBZ) was higher in infan ts (median 48.9%) than in older children (median 14.9% in the 12-15-ye ar-old group). A significant linear correlation with age was found (p < 0.001). In addition to young age, polytherapy (p < 0.01) and adminis tration as a nonretarded formulation rather than as a retarded tablet (p < 0.05) induced a higher relative concentration of the epoxide. The relative concentration of the epoxide did not correlate with the seru m CBZ concentration and the duration of treatment. Although in our stu dy high epoxide levels were not related to clinical side effects, we r ecommend that in very young children polytherapy treatment with carba mazepine should be performed with caution and in difficult cases a det ermination of the epoxide level should be considered.