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 (Cmax) and area under the plasma concentration-time curve from time 0 to infinity (AUCinfinity) were, respectively (arithmetic mean +/- SD), 18.0 +/- 4.6 microg/mL and 325.7 +/- 64.9 microg x h/mL for test 1, 16.0 +/- 4.0 microg/mL and 304.2 +/- 66.0 microg x h/mL for test 2, and 17.0 +/- 4.1 microg/mL and 301.1 +/- 60.0 microg x h/mL for the reference formulation. Point estimate (PE) and 90% confidence intervals (CIs) for AUCinfinity test 1/reference geometric mean ratio were 1.09 and 1.01, 1.15; for Cmax 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 AUCinfinity ratio, and 0.94 and 0.86, 1.02 for the Cmax ratio. Bioequivalence of test versus reference formulations is thus accepted for both AUCinfinity and Cmax 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.
RCT Entities:
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 (Cmax) and area under the plasma concentration-time curve from time 0 to infinity (AUCinfinity) were, respectively (arithmetic mean +/- SD), 18.0 +/- 4.6 microg/mL and 325.7 +/- 64.9 microg x h/mL for test 1, 16.0 +/- 4.0 microg/mL and 304.2 +/- 66.0 microg x h/mL for test 2, and 17.0 +/- 4.1 microg/mL and 301.1 +/- 60.0 microg x h/mL for the reference formulation. Point estimate (PE) and 90% confidence intervals (CIs) for AUCinfinity test 1/reference geometric mean ratio were 1.09 and 1.01, 1.15; for Cmax 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 AUCinfinity ratio, and 0.94 and 0.86, 1.02 for the Cmax ratio. Bioequivalence of test versus reference formulations is thus accepted for both AUCinfinity and Cmax 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.