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Stereoselective disposition of S ‐ and R ‐licarbazepine in mice
Author(s) -
Alves Gilberto,
Figueiredo Isabel,
Falcão Amílcar,
CastelBranco Margarida,
Caramona Margarida,
SoaresDASilva Patrício
Publication year - 2008
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20546
Subject(s) - stereoselectivity , chemistry , metabolite , enantiomer , kidney , disposition , pharmacokinetics , metabolism , chirality (physics) , pharmacology , stereochemistry , medicine , biochemistry , psychology , catalysis , social psychology , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark
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.