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https://hdl.handle.net/10316/10112
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: | 2008 | Publisher: | Wiley Interscience | Citation: | Chirality. 20:6 (2008) 796-804 | Project: | SFRH/12694/2003 | Serial title, monograph or event: | Chirality | Volume: | 20 | Issue: | 6 | 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. Chirality, 2008. © 2008 Wiley-Liss, Inc. | URI: | https://hdl.handle.net/10316/10112 | DOI: | 10.1002/chir.20546 | Rights: | openAccess |
Appears in Collections: | FFUC- Artigos em Revistas Internacionais |
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