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Relative Bioavailability and Bioequivalence of Brivaracetam 10 mg/mL Oral Solution and 50‐mg Film‐Coated Tablet
Author(s) -
Otoul Christian,
Watanabe Shikiko,
McCabe Suzanne,
Stockis Armel
Publication year - 2016
Publication title -
clinical pharmacology in drug development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.711
H-Index - 22
eISSN - 2160-7648
pISSN - 2160-763X
DOI - 10.1002/cpdd.275
Subject(s) - medicine , pharmacokinetics , pharmacology , bioavailability , bioequivalence , crossover study , tolerability , therapeutic index , adverse effect , drug , alternative medicine , pathology , placebo
Brivaracetam was recently approved as adjunctive therapy in the treatment of focal (partial-onset) seizures in patients 16 years of age and older with epilepsy. Brivaracetam is a selective, high-affinity ligand for synaptic vesicle protein 2A.1,2 In phase 2 and 3 studies,3–8 brivaracetam has shown efficacy and good tolerability in adult patients with uncontrolled focal seizures. Brivaracetam pharmacokinetics is doseproportional over a range of doses far exceeding the therapeutic doses.9,10 It is completely absorbed orally (96.8% urinary excretion in mass balance study), shows no food effect, binds weakly to plasma proteins (17.5%), has an apparent volume of distribution corresponding to total body water, and has a plasma half-life of approximately 9 hours.9–11 The major metabolic pathway of brivaracetam involves transformation of the amide function into a carboxylic acid by non-CYP-dependent enzyme amidase EC 3.5.1.4, and a second pathway involves CYP2C19-mediated hydroxylation of the propyl side chain.11–13 An oral solution formulation of brivaracetam has been developed to provide an additional treatment option for patients who have difficulty in swallowing tablets. The objective of this study was to assess the relative bioavailability and bioequivalence of brivaracetam oral solution (10 mg/mL) and brivaracetam 50-mg tablet (reference tablet throughout clinical development) after single administration in healthy participants.