Stereoselective disposition of S- and R-licarbazepine in mice

✍ Scribed by Gilberto Alves; Isabel Figueiredo; Amílcar Falcão; Margarida Castel-Branco; Margarida Caramona; Patrício Soares-DA-Silva

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 168 KB
• Volume: 20
• Category: Article
• ISSN: 0899-0042
• DOI: 10.1002/chir.20546

✦ Synopsis

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.