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Dose Proportionality of Licarbazepine Pharmacokinetics after Single and Repeated Oral Doses in Healthy Volunteers
Author(s) -
Souppart Claire,
Merz Michael,
Balez Sebastien,
Agarwal Anni,
Mercier Francois,
AppelDingemanse Silke
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a417
Subject(s) - pharmacokinetics , cmin , cmax , dosing , medicine , crossover study , pharmacology , anesthesia , placebo , alternative medicine , pathology
Objective: Licarbazepine is being developed for the treatment of bipolar disorder. This study investigated its dose proportional pharmacokinetics and safety in healthy subjects. Methods: In an open‐label, randomized, three‐treatment, three‐period, three‐sequence crossover study, 13 healthy men and women (18‐50 years of age; 2 discontinued and one was replaced) were administered 250, 500, or 1000 mg of licarbazepine orally as a single dose followed by twice daily (bid) administrations for 4.5 days, under fasted conditions. Results: Single‐dose licarbazepine pharmacokinetics were slightly over‐proportional with respect to area under the curve (AUC ∞ ), but were dose proportional for maximum plasma concentration (C max ). Multiple‐dose licarbazepine pharmacokinetics were proportional across the dose range for steady‐state AUC τ ,C max , and C min . The time to C max (1–2 hours) and elimination half‐life (7.6–9.2 hours) were dose independent and did not change substantially with multiple dosing. Steady state was reached after 3 days of bid dosing, and licarbazepine accumulation was approximately 2.5 for all doses. Single and multiple oral doses of 250‐ and 500‐mg licarbazepine were safe and well tolerated; 1000‐mg doses were associated with more adverse events. Conclusions: The favorable pharmacokinetic characteristics of licarbazepine suggest that it may be an easy‐to‐use treatment option for bipolar disorder.