Stereoselective Inversion of (R)-Fenoprofen to (S)-Fenoprofen in Humans

Abstract The concentrations of the ( R )- and ( S )-enantiomers of fenoprofen (α-methyl-3-phenoxy-benzeneacetic acid) were measured in plasma and urine of volunteers after oral administration of the ( R , S )-racemate. In addition, urinary concentrations of the ( R )- and ( S )-4′-hydroxy metabolite of fenoprofen, the major metabolite, were measured. The ( R )-enantiomer of fenoprofen was stereoselectively inverted to ( S )-fenoprofen, which was the major isomeric form found in plasma and urine. A potency comparison of the enantiomers in vitro showed the ( S )-isomer to be 35 times more active than the ( R )-isomer in inhibiting the fatty acid cyclo-oxygenase pathway from human platelets. In vivo, the similar pharmacological potency of the two enantiomers previously observed in experimental animals may have been due to the rapid inversion of the ( R )-to ( S )-isomer.