title: Assessment of the bioequivalence of two oxcarbazepine oral suspensions versus a film-coated tablet in healthy subjects.
abstract: Oxcarbazepine (trileptal) oral suspension has been reformulated and a study was performed to compare the bioavailability after single doses and at steady state of the current and former oral suspension versus the marketed film-coated tablets and to compare the bioavailability of the current and former oral suspension. The results support the switch from the former oral suspension to the current oral suspension and also from both oral suspensions to the film-coated tablet and vice versa. The study was an open-label, single-center, 3-way crossover trial. Each treatment period consisted of a single dose of 600 mg oxcarbazepine on Day 1, 600 mg oxcarbazepine b.i.d. repeated administration from Day 4 up to including Day 7, and a final dose of 600 mg oxcarbazepine administered on the morning of Day 8. Blood samples were taken on Day 1, Day 7 and Day 8 (pre-dose). Plasma concentrations of the main metabolite of oxcarbazepine (MHD) were determined using a validated HPLC assay. The 2 oral suspensions were compared with the film-coated tablet as reference formulation under fasted conditions. Also the current oral suspension was compared with the former oral suspension. These comparisons were made using data following single dose administration and under steady state conditions. Plasma AUC for single dose and AUC(0-12h) at steady state and plasma Cmax, log-transformed (natural base) were used for the assessment of bioequivalence. The 90% confidence interval (CI) approach was used for testing bioequivalence. Bioequivalence was accepted if CI was contained within the region (0.8, 1.25). At steady state, both the former and the current oral suspensions showed bioequivalence with the film-coated tablet with respect to AUC and Cmax. The current oral suspension was also bioequivalent when compared to the former oral suspension with respect to AUC and Cmax. After single dose, the former oral suspension was bioequivalent when compared to the film-coated tablet with respect to both AUC and Cmax. However, the current oral suspension was bioequivalent to both the film-coated tablet and the former oral suspension with respect to AUC but not to Cmax.
authors.affiliation: Clinical Pharmacology, Novartis Pharma AG, Basel, Switzerland. gerard_jp.flesch@pharma.novartis.com
authors.forename: G
authors.initials: G
authors.lastname: Flesch
authors.forename: D
authors.initials: D
authors.lastname: Tudor
authors.forename: J
authors.initials: J
authors.lastname: Denouel
authors.forename: J
authors.initials: J
authors.lastname: Bonner
authors.forename: R
authors.initials: R
authors.lastname: Camisasca
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002220:Carbamazepine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000097:blood; D006207:Half-Life; D006801:Humans; D008297:Male; D000078330:Oxcarbazepine; D013535:Suspensions; D013810:Therapeutic Equivalency
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; D013535:Suspensions; D002220:Carbamazepine; D000078330:Oxcarbazepine; C428744:10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide