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

Stereoselective disposition of flurbiprofen in normal volunteers.

“…In the case of some 'profens', such as ibuprofen and fenoprofen, inter-individual variability in the plasma concentrations of the active S-enantiomer may be accentuated by unidirectional R-to S-inversion (Caldwell & Marsh, 1983;Lee et al, 1985;Rubin et al, …”

The Stereoselectivity of Drug Action

“…Studies carried out in vitro have shown that their (q-enantioners (XLIV and XLV) are far more potent than their antipodes as cyclooxygenase inhibitors. However, no marked difference between anti-inflammatory actions of the (R)-and (3-enantiomers has been observed in vivo, because the less active (@-form is converted to the (3-form by stereoselective enzymatic processes (Adams et al 1976;Rubin et al 1985). The rate and degree of conversion of the less active enantiomer of these anti-inflammatory drugs to the more active one depends on a variety of factors, such as liver and kidney function and stereoselective protein binding (Rendic et al 1980).…”

Chiral inversion of RS‐8359: A selective and reversible MAO‐A inhibitor via oxido‐reduction of keto‐alcohol

“…Skalova et al 24,25 demonstrated that, in addition to chiral inversion at 2-arylpropionic acid of flobufen, its secondary alcohol metabolite, 4-dihydroflobufen, underwent chiral inversion at the alcohol group in primary cultures of human hepatocytes. Walters et al 26 reported chiral inversion of the (S)-enantiomer but not the (R)-enantiomer of lifibrol, a HMG CoA reductase inhibitor, at a secondary alcohol group in dogs. The mechanisms were not yet clarified in detail, but a combination of enantioselective oxidation and subsequent reduction might lead to the unidirectional chiral inversion.…”