Chiral inversion of 2-arylpropionic acid non-steroidal anti-inflammatory drugs--1. In vitro studies of ibuprofen and flurbiprofen

Biochem Pharmacol. 1989 Dec 15;38(24):4389-95. doi: 10.1016/0006-2952(89)90647-3.


The mechanism of inversion of the enantiomers of 2-arylpropionic acids was investigated in vitro using tissue homogenates. Crude rat liver homogenate was shown to mediate the inversion of R to S-ibuprofen, but not inversion of the S to the R-enantiomer. Inversion required CoA and ATP as cofactors. In contrast, R-ibuprofen was not inverted by homogenates of kidney or small intestine and there was no inversion of the enantiomers of flurbiprofen by any of these tissue homogenates. Long-chain acyl-CoA synthetase was partially purified from rat liver microsomes and bound to Matrex Gel Red A. R-Ibuprofen was shown to be a substrate for this enzyme while S-ibuprofen and R and S-flurbiprofen were not substrates. These data are consistent with the hypothesis that the stereospecificity of inversion is controlled by the acyl-CoA synthetase. R-Ibuprofen-CoA did not racemize in either buffer solution (pH 7.4) or human plasma consistent with the hypothesis that racemization of the CoA thioesters is mediated enzymatically.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Flurbiprofen / metabolism*
  • Ibuprofen / metabolism*
  • Intestine, Small / metabolism
  • Isomerism
  • Kidney / metabolism
  • Kinetics
  • Liver / metabolism*
  • Male
  • Rats
  • Rats, Inbred Strains


  • Anti-Inflammatory Agents, Non-Steroidal
  • Flurbiprofen
  • Ibuprofen