Stereoselective inversion of (R)-fenoprofen to (S)-fenoprofen in humans

J Pharm Sci. 1985 Jan;74(1):82-4. doi: 10.1002/jps.2600740122.

Abstract

The concentrations of the (R)- and (S)-enantiomers of fenoprofen (alpha-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.

MeSH terms

  • Biotransformation
  • Blood Platelets / enzymology
  • Cyclooxygenase Inhibitors
  • Fenoprofen / metabolism*
  • Fenoprofen / pharmacology
  • Humans
  • Hydroxylation
  • In Vitro Techniques
  • Male
  • Phenylpropionates / metabolism*
  • Stereoisomerism
  • Time Factors

Substances

  • Cyclooxygenase Inhibitors
  • Phenylpropionates
  • Fenoprofen