title: A Pharmacokinetic Study Comparing Eslicarbazepine Acetate Administered Orally as a Crushed or Intact Tablet in Healthy Volunteers.
abstract: 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-∞) and Cmax 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 Cmax , 11 700 versus 11 500 ng/mL; AUC(0-∞) , 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 (Cmax , 102.63% [97.07%-108.51%]; AUC(0-∞) , 96.72% [94.36%-99.13%]; AUC0-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.
authors.affiliation: Sunovion Pharmaceuticals Inc, Marlborough, MA, USA.
authors.forename: Soujanya
authors.initials: S
authors.lastname: Sunkaraneni
authors.affiliation: Infinity Pharmaceuticals Inc, Cambridge, MA, USA.
authors.forename: Jahnavi
authors.initials: J
authors.lastname: Kharidia
authors.affiliation: Quintiles, Overland Park, KS, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: Schutz
authors.affiliation: Sunovion Pharmaceuticals Inc, Marlborough, MA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.affiliation: Sunovion Pharmaceuticals Inc, Marlborough, MA, USA.
authors.forename: Hailong
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; D013607:Tablets; C416835:eslicarbazepine acetate; C428744:10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide
keywords: clinical trials (CTR); drug delivery (DEL); epilepsy; eslicarbazepine acetate; pharmacokinetics and drug metabolism