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Stereoselective Disposition of S- and R-Licarbazepine in Mice

By Gilberto Alves, Isabel Figueiredo, Amílcar Falcão, Margarida Castel-Branco, Margarida Caramona and Patrício Soares-da-Silva


The stereoselective disposition of S-licarbazepine (S-Lic) and R-licarbazepine (R-Lic) was investigated in plasma, brain, liver, and kidney tissues after their individual administration (350 mg/kg) to mice by oral gavage. Plasma, brain, liver, and kidney concentrations of licarbazepine enantiomers and their metabolites were determined over the time by a validated chiral HPLC-UV method. The mean concentration data, attained at each time point, were analyzed using a non-compartmental model. S-Lic and R-Lic were rapidly absorbed from gastrointestinal tract of mouse and immediately distributed to tissues supplied with high blood flow rates. Both licarbazepine enantiomers were metabolized to a small extent, each parent compound being mainly responsible for the systemic and tissue drug exposure. The stereoselectivity in the metabolism and distribution of S- and R-Lic was easily identified. An additional metabolite was detected following R-Lic administration and S-Lic showed a particular predisposition for hepatic and renal accumulation. Stereoselective processes were also identified at the blood–brain barrier, with the brain exposure to S-Lic almost twice that of R-Lic. Another finding, reported here for the first time, was the ability of the mouse to perform the chiral inversion of S- and R-Lic, albeit to a small extent

Topics: stereoselectivity, licarbazepine enantiomers, eslicarbazepine acetate, oxcarbazepine, pharmacokinetics, chiral separation, mouse plasma, mouse tissues
Publisher: 'Wiley'
Year: 2008
DOI identifier: 10.1002/chir.20546
OAI identifier:
Provided by: Estudo Geral

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