Bioequivalence of oxcarbazepine oral suspension vs. film-coated tablet in healthy Chinese male subjects.
OBJECTIVE
Oxcarbazepine (Trileptal) is an antiepileptic drug used as monotherapy or adjunctive therapy in the treatment of partial seizures in adults and children. The primary objective of this study was to assess the bioequivalence of Trileptal oral suspension formulation vs. the film-coated tablet after single and multiple twice-daily administrations in fasted, healthy Chinese male subjects.


METHODS
This was an open-label, randomized, two-period crossover study in 19 healthy Chinese male subjects. Treatment periods consisted of a single dose of 300 mg oxcarbazepine (either oral suspension formulation or film-coated tablet) on Day 1, b.i.d. administrations of 300 mg from Day 4 to Day 8 inclusive, and a final dose of 300 mg on the morning of Day 9. A 1-week washout period was implemented between treatment periods. Plasma levels of 10-monohydroxy derivative (MHD), the main metabolite mediating the pharmacologic activity of oxcarbazepine, were measured by a validated liquid chromatography tandem mass spectrometry method. Bioequivalence was assessed by the MHD areas under the concentration time curve (AUCs) and maximum concentrations (Cmax) of the oral suspension vs. the film-coated tablet. Safety was evaluated throughout the study.


RESULTS
Trileptal oral suspension formulation was bioequivalent to film-coated tablet after single dose and multiple b.i.d. administrations, as assessed by MHD AUCs and Cmax. The 90% confidence intervals (CI) of the geometric mean of the MHD individual ratios were within the bioequivalence CI limits (0.80 - 1.25). No safety concerns were raised.


CONCLUSIONS
Trileptal oral suspension formulation and film-coated tablets are bioequivalent in healthy Chinese males.
Souppart
C
C
Novartis Pharma AG, Basel, Switzerland. claire.souppart@novartis.com
Yin
Q
Q
Merz
M
M
Hu
P
P
Jiang
J
J
Appel-Dingemanse
S
S
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002220:Carbamazepine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine; D013535:Suspensions; D013608:Tablets, Enteric-Coated; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
D000927:Anticonvulsants; D013535:Suspensions; D013608:Tablets, Enteric-Coated; D002220:Carbamazepine; D000078330:Oxcarbazepine