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 responsible for side-effects of CBZ treatment. Fifty-two children between the age of 2 weeks and 15 years were treated 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 solution, 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 with random timing after the last ingestion of the drug. The relative concentration of CBZ epoxide (expressed in % of CBZ) was higher in infants (median 48.9%) than in older children (median 14.9% in the 12-15-year-old group). A significant linear correlation with age was found (p < 0.001). In addition to young age, polytherapy (p < 0.01) and administration 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 serum CBZ concentration and the duration of treatment. Although in our study high epoxide levels were not related to clinical side effects, we recommend that in very young children polytherapy treatment with carbamazepine should be performed with caution and in difficult cases a determination of the epoxide level should be considered.
Korinthenberg
R
R
Department of Neuropediatrics, University Children's Hospital, Freiburg, Germany.
Haug
C
C
Hannak
D
D
D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002657:Child Development / Q000502:physiology*; D002675:Child, Preschool; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy; D017029:Epilepsy, Complex Partial / Q000097:blood / Q000188:drug therapy; D004830:Epilepsy, Tonic-Clonic / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D002220:Carbamazepine; C012227:carbamazepine epoxide