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

1. The extent and the overall stereoselectivity of the combined steps invol ved in the chiral inversion of fenoprofen, a non-steroidal anti-inflammator y drug, was investigated in rat brain microsomes and cytosol. Results were compared with those obtained with the same liver subcellular compartments. 2. Brain microsomes catalysed the stereoselective activation of the R(-)-en antiomer to its coenzyme A thioester with a specific activity similar to 10 -fold less than that obtained with liver microsomes. 3. Rat brain microsomes and cytosol mediated the racemization and hydrolysi s of both R(-)- and S(+)-fenoprofenoyl-CoA. In brain fractions the epimeras e activity was lower than in liver, whereas the hydrolysis process appeared more efficient. 4. 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.