Carbamazepine Population Pharmacokinetics in Children
D. Santos Buelga, M.F. Delgado Iribarnegaray, M.J. Garca, M.J. Otero, A. Falcao, A. Dominguez-Gil
Department of Pharmacy and Pharmaceutical Tecnology, Faculty of Pharmacy. University of Salamanca. Salamanca. Spain
The objective of this study was to describe the pharmacokinetics of carbamazepine (CBZ) in pediatric patients who received CBZ (Tegretol) as an anticonvulsivant using NONMEM, a computer program designed for population PK analysis.
A total of 175 measured serum CBZ concentrations were obtained from 79 patients. There were 39 female and 38 male children whith a total weight ranged from 5 to 69 Kg and age ranged from 2 to 14 years.
Steady-state trough CBZ serum concentrations, CBZ dosing history, concomitant drug administration, and other data from children were collected retrospectively. A one-compartment model with first order absorption and first-order elimination was used, with absorption rate an bioavailability fixed to literature values.
The influence of sex, age, weight and concomitant therapy (Phenobarbitone, Phenytoin and Sodium valproate) were investigated. No evidence was found that sex, and politherapy significantly affected CBZ clearance. In the final model, clearance was based on total body weight and age. The coefficient of variation for clearance estimates was 24%. Estimates for volume of distribution could not be pursued rigorously because of the nature of data, that is why during estimation its value was constrained between 0.5 to 3 l/Kg and was described using a linear relationship with the weight. Residual variability, according an additive model was 0.87 mg/l.
The identification of several patient factors and the quantification of their influence on CBZ disposition can be used to individualize the therapy. These results may assist in the design and adjustment of CBZ dosage schedules in epileptic children.