Dosage Form Proportionality and Food Effect of the Final Tablet Formulation of Eslicarbazepine Acetate

Objective: To investigate the dosage form proportionality and food effect of the final tablet formulation of eslicarbazepine acetate (ESL) in healthy volunteers. Methods: This was a randomized, three-way crossover, single-centre study in 18 healthy volunteers. Subjects received a single dose of oral ESL 800 mg following a standard meal in one period, and following 10 hours of fasting in two separate periods (in the form of one 800 mg tablet [reference] or two 400 mg tablets [test]). The statistical method was based upon the 90% confidence interval (CI) of maximum observed plasma drug concentration (C max ), area under the plasma concentration time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the lower limit of quantification (AUC t ) and AUC from time zero to infinity (AUC ∞ ) geometric means ratios (GMRs) of BIA 2-005, the enantiomeric mixture of the ESL active metabolite eslicarbazepine and its enantiomer R-licarbazepine. Bioequivalence was assumed when the 90% CI of the test/reference GMR fell within the bioequivalence acceptance interval (80.00, 125.00). Results: Following a single dose of ESL 800 mg in the forms of two 400 mg tablets and one 800 mg tablet, the test/reference GMR (%) and 90% CI for C max , AUC t and AUC ∞ were 100.78% (93.91, 108.16), 100.37% (97.82, 102.99) and 100.48% (97.91, 103.13), respectively. Following administration of one 800 mg tablet in fed (test) and fasting (reference) conditions, the test/reference GMR and 90% CI for C max , AUCt and AUC8 were 100.96% (94.08, 108.35), 96.79% (94.34, 99.32) and 96.75% (94.27, 99.29), respectively. Treatments were well tolerated. Conclusions: The bioequivalence criteria between the ESL 400 mg and 800 mg tablets were met and dosage form proportionality was demonstrated. The presence of food had no influence on ESL pharmacokinetics, indicating that ESL can be administered without regard to meals with no significant effects on drug disposition or extent of systemic exposure.