OBJECTIVE: To investigate the effect of food on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093), a new voltage-gated sodium channel antagonist. MATERIAL AND METHODS: Single-centre, open-label, randomised, two-way crossover study in 12 healthy subjects. The study consisted of two consecutive treatment periods separated by a washout of 14 days or more. In each of the study periods subjects were administered a single dose of eslicarbazepine acetate 800 mg following either a standard high-fat content meal or 10 hours of fasting. RESULTS:Eslicarbazepine acetate was rapidly and extensively metabolised to BIA 2-005. Maximum BIA 2-005 plasma concentrations (C(max)) in fed (test) and fasting (reference) conditions were, respectively, 12.8 +/- 1.8 microg/mL and 11.3 +/- 1.9 microg/mL, and the areas under the plasma concentration time curve from 0 to infinity (AUC(infinity)) were, respectively, 242.5 +/- 32.1 microg.h/mL and 243.6 +/- 31.1 microg.h/mL (arithmetic mean +/- SD). The point estimate (PE) and 90% confidence interval (90% CI) of the test/reference C(max )geometric mean ratio were 1.14 and 1.04, 1.25, respectively; for the AUC(infinity) ratio, the PE and 90% CI were 1.00 and 0.95, 1.04, respectively. Bioavailability of eslicarbazepine acetate administered in fed and fasting conditions was similar and bioequivalence is accepted for both AUC(infinity) and C(max) because the 90% CI lies within the acceptance range of 0.80-1.25. No statistically significant differences were found in time of occurrence of C(max). CONCLUSION: The presence of food had no significant effect on the pharmacokinetics of eslicarbazepine acetate and therefore this new voltage-gated sodium channel antagonist may be administered without regard to meals.
RCT Entities:
OBJECTIVE: To investigate the effect of food on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093), a new voltage-gated sodium channel antagonist. MATERIAL AND METHODS: Single-centre, open-label, randomised, two-way crossover study in 12 healthy subjects. The study consisted of two consecutive treatment periods separated by a washout of 14 days or more. In each of the study periods subjects were administered a single dose of eslicarbazepine acetate 800 mg following either a standard high-fat content meal or 10 hours of fasting. RESULTS:Eslicarbazepine acetate was rapidly and extensively metabolised to BIA 2-005. Maximum BIA 2-005 plasma concentrations (C(max)) in fed (test) and fasting (reference) conditions were, respectively, 12.8 +/- 1.8 microg/mL and 11.3 +/- 1.9 microg/mL, and the areas under the plasma concentration time curve from 0 to infinity (AUC(infinity)) were, respectively, 242.5 +/- 32.1 microg.h/mL and 243.6 +/- 31.1 microg.h/mL (arithmetic mean +/- SD). The point estimate (PE) and 90% confidence interval (90% CI) of the test/reference C(max )geometric mean ratio were 1.14 and 1.04, 1.25, respectively; for the AUC(infinity) ratio, the PE and 90% CI were 1.00 and 0.95, 1.04, respectively. Bioavailability of eslicarbazepine acetate administered in fed and fasting conditions was similar and bioequivalence is accepted for both AUC(infinity) and C(max) because the 90% CI lies within the acceptance range of 0.80-1.25. No statistically significant differences were found in time of occurrence of C(max). CONCLUSION: The presence of food had no significant effect on the pharmacokinetics of eslicarbazepine acetate and therefore this new voltage-gated sodium channel antagonist may be administered without regard to meals.