Stereoselective Disposition of S- and R-Licarbazepine in Mice

• Author(s): Alves, Gilberto ; Figueiredo, Isabel ; Falcão, Amílcar ; Castel-Branco, Margarida ; Caramona, Margarida ; Soares-da-Silva, Patrício
• Date: 2008
• Persistent ID: http://hdl.handle.net/10316/2808
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): stereoselectivity; licarbazepine enantiomers; eslicarbazepine acetate; oxcarbazepine; pharmacokinetics; chiral separation; mouse plasma; mouse tissues
• Document Type: Article
• Language: English

Description

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.