Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093), a new voltage-gated sodium channel blocker.
OBJECTIVE
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 (C(max)) and area under the plasma concentration-time curve over 24 h (AUC(0-24)) and from 0 to infinity (AUC(0-infinity)) were, respectively, 9.3 microg/ml, 128.5 microg h/ml and 171.9 microg h/ml in male subjects and 10.1 microg/ml, 150.1 microg h/ml and 205.0 microg h/ml in female subjects. At steady-state, C(max), AUC(0-24) and AUC(0-infinity) were 15.5 microg/ml, 207.8 microg h/ml and 295.8 microg h/ml in male subjects, and 16.8 microg/ml, 214.5 microg h/ml and 295.2 microg h/ml in female subjects. Steady-state plasma concentrations were attained at 4 to 5 days of administration in both groups. Eslicarbazepine C(max), AUC(0-24) and AUC(0-infinity) 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.


CONCLUSIONS
At steady-state, the pharmacokinetic profile of eslicarbazepine acetate was not affected by gender.
Falcão
Amílcar
A
Department of Research and Development, BIAL, 4745-457 S Mamede do Coronado, Portugal.
Maia
Joana
J
Almeida
Luis
L
Mazur
Dago
D
Gellert
Manfred
M
Soares-da-Silva
Patrício
P
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002853:Chromatography, Liquid; D003984:Dibenzazepines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D012737:Sex Factors; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013607:Tablets
D003984:Dibenzazepines; D026941:Sodium Channel Blockers; D013607:Tablets; C416835:eslicarbazepine acetate