Carbamazepine Plasma Levels in Children and Adults

Abstract

The effects of dose/kg, age and associated therapy on carbamazepine (CBZ) plasma concentrations and level/dose (L/D) ratios were evaluated retrospectively on 567 consecutive routine CBZ determinations from 326 chronically treated epileptic patients (207 children and adolescents less than 19 yr old and 119 adults between 19-45 yr of age). In the pediatric group there was no correlation between the administered CBZ dose and the plasma levels. In the adults the correlation was significant but the wide scattering of the plasma concentrations at each given dose was such that the relationship had no predictive value. The CBZ L/D ratio increased linearly with age in patients up to 19 yr. Significant differences in mean CBZ L/D ratios were found between patients aged 0-3 yr, 4-9 yr, 10-15 yr and adults (19-45 yr). The adolescents (16-18 yr) had a mean CBZ L/D ratio very similar to the adults. Associated antiepileptic therapy affected the CBZ L/D ratio, which was significantly reduced in patients also receiving phenytoin, primidone and phenobarbital, as compared to those on CBZ monotherapy. The effects of age and associated therapy on the CBZ L/D ratio were also statistically significant in subgroups homogeneous for associated therapy and age. In subjects > 4 yr of age, a significant negative correlation was observed between CBZ daily D/kg and L/D ratios, suggesting an impaired absorption of CBZ at high doses. The great interindividual variability in CBZ L/D ratios in chronically-treated epileptic patients was confirmed. Because it is impossible to predict the plasma concentrations that will be attained in individual patients after a given dose, routine monitoring of CBZ plasma levels is very useful, especially in pediatric patients and in patients on polytherapy.