Mutual inversion of flurbiprofen enantiomers in various rat and mouse strains

Chirality. 2018 May;30(5):632-641. doi: 10.1002/chir.22826. Epub 2018 Feb 6.


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, FI = 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, FI = 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.

Keywords: (R)-flurbiprofen (RF); (S)-flurbiprofen (SF); enantiomers; experimental autoimmune encephalomyelitis (EAE); α-methylacyl-CoA racemase (AMACR).

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Female
  • Flurbiprofen / chemistry*
  • Flurbiprofen / pharmacokinetics*
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Racemases and Epimerases / genetics
  • Rats, Inbred Lew
  • Stereoisomerism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Flurbiprofen
  • Racemases and Epimerases
  • alpha-methylacyl-CoA racemase