Title: Stereoselective Disposition of S- and R-Licarbazepine in Mice
Authors: Alves, Gilberto 
Figueiredo, Isabel 
Falcão, Amílcar 
Castel-Branco, Margarida 
Caramona, Margarida 
Soares-da-Silva, Patrício 
Keywords: stereoselectivity;licarbazepine enantiomers;eslicarbazepine acetate;oxcarbazepine;pharmacokinetics;chiral separation;mouse plasma;mouse tissues
Issue Date: 10-Jan-2008
Publisher: Wiley Interscience
Citation: ALVES, Gilberto et al. - Stereoselective Disposition of S- and R-Licarbazepine in Mice. CHIRALITY 20 (2008) 796–804
Abstract: 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.
URI: http://hdl.handle.net/10316/2808
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais

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