A Pharmacokinetic Study Comparing Eslicarbazepine Acetate Administered Orally as a Crushed or Intact Tablet in Healthy Volunteers

The relative bioequivalence of crushed versus intact eslicarbazepine acetate (ESL) tablets (800 mg) administered orally in healthy adults was evaluated in an open-label, randomized, 2-period crossover study with a 5-day washout between treatments. Sample blood levels of eslicarbazepine and (R)-licarbazepine were determined; pharmacokinetic parameters were derived for eslicarbazepine. Bioequivalence was established if the 90% confidence intervals (CIs) for the geometric mean treatment ratios of eslicarbazepine AUC((0-infinity)) and C-max were within the prespecified 80%-125% range. Twenty-seven subjects in the intent-to-treat population (n = 28) completed both treatment periods. Eslicarbazepine exposure measures were similar for crushed versus intact ESL tablets: average C-max, 11 700 versus 11 500 ng/mL; AUC((0-infinity)), 225 000 versus 234 000 ng.h/mL; AUC((0-last)), 222 000 versus 231 000 ng.h/mL, respectively. Geometric least squares mean ratios ( 90% CIs) comparing eslicarbazepine exposure measures were within the 80%-125% range (C-max, 102.63% [97.07%-108.51%]; AUC((0-infinity)), 96.72% [94.36%-99.13%]; AUC(0-last), 96.69% [94.24%-99.21%]). In conclusion, ESL administered orally as a crushed tablet sprinkled on applesauce, or intact were bioequivalent in healthy subjects. Eslicarbazepine bioavailability was not significantly altered by crushing, indicating that ESL tablets can be administered intact or crushed.