Effect of Gender on the Pharmacokinetics of Eslicarbazepine Acetate (BIA 2-093), a New Voltage-gated Sodium Channel Blocker

Abstract

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, oncedaily, 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 1) were, respectively, 9.3 mg/ml, 128.5 mg h/ml and 171.9 mg h/ml in male subjects and 10.1 mg/ml, 150.1 mg h/ml and 205.0 mg h/ml in female subjects. At steady-state, Cmax, AUC0 24 and AUC0 1 were 15.5 mg/ml, 207.8 mg h/ml and 295.8 mg h/ml in male subjects, and 16.8 mg/ml, 214.5 mg h/ml and 295.2 mg 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 1 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.