In vitro study of fenoprofen chiral inversion in rat: comparison of brain versus liver

The extent and the overall stereoselectivity of the combined steps involved in the chiral inversion of fenoprofen, a non-steroidal anti-inflammatory drug, was investigated in rat brain microsomes and cytosol. Results were compared with those obtained with the same liver subcellular compartments. Brain microsomes catalysed the stereoselective activation of the R(-)-enantiomer to its coenzyme A thioester with a specific activity approximately 10-fold less than that obtained with liver microsomes. Rat brain microsomes and cytosol mediated the racemization and hydrolysis of both R(-)- and S( + )-fenoprofenoyl-CoA. In brain fractions the epimerase activity was lower than in liver, whereas the hydrolysis process appeared more efficient. Thus, the data indicated that the three-step mechanism occurred in brain subcellular compartments leading to a minor chiral inversion of fenoprofen compared with that in liver.