Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093), a new voltage-gated sodium channel blocker

Purpose. To determine the effect of gender on the pharmacokinetics of eslicarbazepine acetate, a novel voltage‐gated sodium channel blocker in the development for the treatment of epilepsy and bipolar disorder. Methods. Single‐centre, open‐label, parallel‐group study in 12 female and 12 male healthy subjects. The study consisted of a single‐dose (600 mg) period and a multiple‐dose (600 mg, once‐daily, for 8 days) period, separated by 4 days. Results. Eslicarbazepine acetate was rapidly and extensively metabolized to eslicarbazepine (S‐licarbazepine), the main active metabolite. Following a single‐dose, arithmetic mean eslicarbazepine maximum plasma concentrations (Cmax) and area under the plasma concentration‐time curve over 24 h (AUC0−24) and from 0 to infinity (AUC0−∞) were, respectively, 9.3 µg/ml, 128.5 µg h/ml and 171.9 µg h/ml in male subjects and 10.1 µg/ml, 150.1 µg h/ml and 205.0 µg h/ml in female subjects. At steady‐state, Cmax, AUC0−24 and AUC0−∞ were 15.5 µg/ml, 207.8 µg h/ml and 295.8 µg h/ml in male subjects, and 16.8 µg/ml, 214.5 µg h/ml and 295.2 µg h/ml in female subjects. Steady‐state plasma concentrations were attained at 4 to 5 days of administration in both groups. Eslicarbazepine Cmax, AUC0−24 and AUC0−∞ female:male geometric mean ratios (90%CI) were, respectively, 1.09 (0.94; 1.24), 1.16 (1.00; 1.33) and 1.17 (0.99; 1.38) following single‐dose, and 1.10 (0.97; 1.25), 1.04 (0.92; 1.17) and 1.01 (0.88; 1.16) at steady‐state. Conclusion. At steady‐state, the pharmacokinetic profile of eslicarbazepine acetate was not affected by gender. Copyright © 2007 John Wiley & Sons, Ltd.