REPLACING CARBAMAZEPINE SLOW-RELEASE TABLETS WITH CARBAMAZEPINE SUPPOSITORIES - A PHARMACOKINETIC AND CLINICAL-STUDY IN CHILDREN WITH EPILEPSY

A suppository for rectal administration of carbamazepine has been deve loped for situations in which it is unsuitable to use the oral route o f administration. In an open, controlled, within-patient study, the ph armacokinetics, clinical efficacy, and tolerability of carbamazepine s low-release tablets were compared with those of carbamazepine supposit ories in children with epilepsy. The pharmacokinetic part of the study comprised 22 children, and an additional nine children were included in the clinical part of the study. Treatment with slow-release tablets was replaced for 7 days with carbamazepine suppositories in bioequiva lent dosage. Clinical factors such as the rate of seizures and the loc al tolerability were studied, and an overall assessment of efficacy wa s made. In the pharmacokinetic part, 24-hour plasma concentration curv es for carbamazepine and carbamazepine-10,11-epoxide were recorded. Th e plasma concentration profiles (minimum, maximum, and mean concentrat ions, fluctuation index, and area under the curve) for carbamazepine a nd the other metabolites did not show any significant differences betw een oral and rectal administration when the suppository dose was incre ased by 25% compared to the tablets. No increase in seizure frequency was detected, and the overall assessment was very good to good in 25 o f the 29 epileptic children. Increased flatulence during treatment wit h suppositories was noted in two children, one had anal irritation, an d one had nausea/vomiting. Treatment with carbamazepine slow-release t ablets in children with epilepsy can be replaced by carbamazepine supp ositories in 25% higher dosage, with good clinical effect and appropri ate pharmacokinetic values, when it is unsuitable to use the common or al route of administration.