Implications of metabolic parameters of carbamazepine in the therapeutic monitoring of Tunisian patients with epilepsy

Carbamazepine (CBZ) is widely used in the control of simple and complex focal seizures and generalized tonic-clonic seizures in patients with epilepsy. The toxic effects of CBZ are not easily predicted, and this is due to the difficulty of delivering the optimal dose and/or plasma concentration of CBZ necessary to achieve beneficial effects, and especially to prevent the onset of toxicity associated with its use. Our study aimed to determine the relationship between the administered daily dose of CBZ and its pharmacokinetic parameters, including concentrations of CBZ and carbamazepine-10,11-epoxide (CBZ-E) plasma levels, and the metabolic ratio of CBZ-E to CBZ, in Tunisian patients with epilepsy. To accomplish this, a high-performance liquid chromatography method with ultraviolet detection was used for quantification in the simultaneous analysis of CBZ and one of its active metabolites, CBZ-E, in human plasma. A statistically significant positive correlation was found between the daily doses administered (mg/kg/day) and plasma concentrations of CBZ and CBZ-E, and the CBZ-E/CBZ ratio increased significantly as a function of the specific dose (in mg/kg/day). The increase in plasma concentrations of CBZ-E was non-linear in relation to plasma concentrations of CBZ, and there was no correlation between the CBZ-E/CBZ metabolic ratio and CBZ plasma concentrations. Our findings suggest that monitoring of CBZ as well as CBZ-E blood levels should be considered, as it may play a useful role in the therapeutic management of patients with epilepsy.