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, 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.

CONCLUSION:

At steady-state, the pharmacokinetic profile of eslicarbazepine acetate was not affected by gender.

• Authors: Amílcar Falcão, Joana Maia, Luis Almeida, Dago Mazur, Manfred Gellert, Patrício Soares-da-Silva
• Journal: Biopharmaceutics & drug disposition (Biopharm Drug Dispos) Vol. 28 Issue 5 Pg. 249-56 (Jul 2007) ISSN: 0142-2782 [Print] England
• PMID: 17443646 (Publication Type: Clinical Trial, Journal Article)
• Copyright: Copyright (c) 2007 John Wiley & Sons, Ltd.

Chemical References

• Dibenzazepines
• Sodium Channel Blockers
• Tablets
• eslicarbazepine acetate

Topics

• Administration, Oral
• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Area Under Curve
• Chromatography, Liquid
• Dibenzazepines (administration & dosage, blood, pharmacokinetics)
• Female
• Half-Life
• Humans
• Male
• Mass Spectrometry
• Middle Aged
• Sex Factors
• Sodium Channel Blockers (administration & dosage, blood, pharmacokinetics)
• Tablets