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

Biopharm Drug Dispos. 2007 Jul;28(5):249-56. doi: 10.1002/bdd.549.

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.

Publication types

  • Clinical Trial

MeSH terms

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

Substances

  • Dibenzazepines
  • Sodium Channel Blockers
  • Tablets
  • eslicarbazepine acetate