Premium
Stereoselective and species‐dependent kinetics of reboxetine in mouse and rat
Author(s) -
Benedetti Margherita Strolin,
Frigerio Enrico,
Tocchetti Paola,
Brianceschi Giannantonio,
Castelli Maria Grazia,
Pellizzoni Cinzia,
Dostert Philippe
Publication year - 1995
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.530070416
Subject(s) - chemistry , enantiomer , reboxetine , bioavailability , pharmacology , stereoselectivity , high performance liquid chromatography , derivatization , chromatography , stereochemistry , biochemistry , serotonin , medicine , receptor , reuptake inhibitor , catalysis
Reboxetine, (RS)‐2‐[(RS)‐α‐(2‐ethoxyphenoxy)benzyl]morpholine methanesulphonate, is a racemic compound and consists of a mixture of the (R,R)‐ and (S,S)‐enantiomers. In this study, brain and plasma levels of both enantiomers were determined in mice and rats after oral administration of reboxetine at doses (1.1 mg/kg, mouse; 20 mg/kg, rat) twice the respective ED 50 values in the antireserpine test. Plasma and brain concentrations of each enantiomer were measured up to 6 h postdosing using an HPLC method with fluorimetric detection after derivatization with a chiral agent (FLEC). In mice and rats, brain and plasma levels of the (R,R)‐enantiomer were always higher than those of the (S,S)‐enantiomer. After normalization for dose, the mean AUC 0‐tz values of both the (R,R)‐ and (S,S)‐enantiomers in mouse brain were about 23 and 32 times higher than in rat brain, respectively. In plasma, the corrected mean AUC 0‐tz values were about 5 (R,R) and 10 (S,S) times higher in mice than in rats. These results provide evidence for the higher bioavailability and/or lower clearance of both enantiomers in mice than in rats, and for a higher penetration of both enantiomers into mouse brain compared to rat brain. © 1995 Wiley‐Liss, Inc.