Pharmacokinetic study of carbamazepine and its carbamazepine 10,11-epoxide metabolite in a group of female epileptic patients under chronic treatment

Abstract

Background Although epileptic crises are equally frequent in women and men, several factors cause female epileptics to present a series of gender-specific problems. To date, few studies have been published on the kinetics of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-E) active metabolite in a Mexican population, and no information for epileptic women of reproductive age is available. The aim of the present work was to study the pharmacokinetic behavior of this group of women during steady state. Methods Fourteen epileptic women under chronic treatment receiving only the anticonvulsant CBZ to control their crises were studied. A blood sample was taken before breakfast, before the morning dose of 200 mg, and after the dose at 1, 2, 3, 4, 5, and 8 h. Serum was separated by centrifugation at 1,350× g. Serum concentrations of carbamazepine (CBZ) and of the metabolite carbamazepine 10,11-epoxide (CBZ-E) were measured by HPLC. Pharmacokinetic parameters were calculated by statistical moment method after obtaining serum concentrations. Results Maximum time (T max) for CBZ was reached at 2.72±0.71 h and for CBZ-E, it was 3.60±0.79 h. C max for CBZ was 7.30±2.30 μg/mL, while C min for CBZ was 6.30±2.49. Maximum serum values for CBZ-E were 1.01±0.57, equivalent to 13.80% of CBZ; t 1 2 value for CBZ and CBZ-E was 18.20 and 16.10 h, respectively. AUC values for CBZ and metabolite were 70.33±17.10 μg/L/h and 9.20±2.50 μg/L/h, respectively. CBZ and CBZ-E clearance did not show differences and were 0.37 mL/kg/min and 0.40 mL/kg/min, respectively. Extraction index for serum concentrations of CBZ and CBZ-E AUC CBZ/AUC CBZ-E was 0.13; positive correlation was observed between serum concentrations of CBZ and E-CBZ, with r = 0.94. Conclusions The schedule we suggest for therapeutic monitoring of serum concentrations of CBZ in chronic treatments is 3 h for maximum peak concentration of C max after dose administration and for minimum peak concentration, C min prior to subsequent administration of the dose.