Premium
Mutual inversion of flurbiprofen enantiomers in various rat and mouse strains
Author(s) -
Bruin Natasja,
Ferreirós Nerea,
Schmidt Mike,
Hofmann Martine,
Angioni Carlo,
Geisslinger Gerd,
Parnham Michael John
Publication year - 2018
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.22826
Subject(s) - flurbiprofen , enantiomer , chemistry , inversion (geology) , stereochemistry , nonsteroidal , pharmacology , biology , paleontology , structural basin
Flurbiprofen (F) is a nonsteroidal anti‐inflammatory drug (NSAID) used therapeutically as the racemate of ( R )‐enantiomer and ( S )‐enantiomer. The inversion of RF to SF and vice versa was investigated in C57Bl/6 and SJL mice and Dark Agouti and Lewis rats. The enzyme α‐methylacyl‐CoA racemase (AMACR) is involved in the chiral inversion pathway that converts members of the 2‐arylpropionic acid NSAIDs from the R‐enantiomer to the S‐enantiomer. We studied C57Bl/6 mice deficient in AMACR postulating that they should show reduced inversion of RF to SF. In line with the data of others in mice, ( R )‐inversion to ( S )‐inversion was relatively high in both the C57Bl/6 and SJL mice (fraction inverted, F I = 37.7% and 24.7%, respectively). In contrast, in AMACR deficient mice, there was no measurable peak for SF after administration of RF. The results in both rat strains (Dark Agouti and Lewis rats, F I = 1.4% and 4.1%, respectively) confirm the low chiral inversion of the enantiomers of flurbiprofen in the rat, as observed by other authors in the Sprague‐Dawley strain (<5%). From the present results, we conclude that for the study of flurbiprofen enantiomers, the rat is more suitable than the mouse as a model for the human in which ( R )‐inversion to ( S )‐inversion is negligible.