Eslicarbazepine Acetate (BIA 2-093)

Abstract

Purpose: To investigate the bioavailability and bioequivalence of three different formulations of eslicarbazepine acetate (BIA 2-093): 50 mg/mL oral suspension (test 1), 200mg tablets (test 2) and 800mg tablets (reference).

Design, subjects and methods: Single-centre, open-label, randomised, three-way crossover study in 18 healthy subjects. The study consisted of three consecutive periods separated by a washout period of 7 days or more. Each subject received a single dose of eslicarbazepine acetate 800mg on three different occasions: 16mL of oral 50 mg/mL suspension, four 200mg tablets or one 800mg tablet.

Results: Eslicarbazepine acetate was rapidly and extensively metabolised to BIA 2-005. Maximum BIA 2-005 plasma concentrations (C_max) and area under the plasma concentration-time curve from time 0 to infinity (AUC_∞) were, respectively (arithmetic mean ± SD), 18.0 ± 4.6 μg/mL and 325.7 ± 64.9 μg · h/mL for test 1, 16.0 ± 4.0 μg/mL and 304.2 ± 66.0 μg · h/mL for test 2, and 17.0 ± 4.1 μg/mL and 301.1 ± 60.0 μg · h/mL for the reference formulation. Point estimate (PE) and 90% confidence intervals (CIs) for AUC_∞ test 1/reference geometric mean ratio were 1.09 and 1.01, 1.15; for C_max ratio, PE and 90% CI were 1.07 and 0.97, 1.15. When test 2 and the reference formulations were compared, the PE and 90% CI were 0.99 and 0.94, 1.07 for the AUC_∞ ratio, and 0.94 and 0.86, 1.02 for the C_max ratio. Bioequivalence of test versus reference formulations is thus accepted for both AUC_∞ and C_max because the 90% CIs lie within the acceptance range of 0.80–1.25.

Conclusion: The pharmacokinetic profiles of eslicarbazepine acetate oral 50 mg/mL suspension, 200mg tablet and 800mg tablet formulations were essentially similar, and the formulations can be considered bioequivalent.