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Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2‐093), a new voltage‐gated sodium channel blocker
Author(s) -
Falcão Amílcar,
Maia Joana,
Almeida Luis,
Mazur Dago,
Gellert Manfred,
SoaresdaSilva Patrício
Publication year - 2007
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.549
Subject(s) - pharmacokinetics , sodium channel blocker , area under the curve , plasma concentration , sodium channel , active metabolite , metabolite , medicine , pharmacology , chemistry , sodium , organic chemistry
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 ( C max ) and area under the plasma concentration‐time curve over 24 h ( AUC 0−24 ) and from 0 to infinity ( AUC 0−∞ ) 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, C max , AUC 0−24 and AUC 0−∞ 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 C max , AUC 0−24 and AUC 0−∞ 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.