Ibuprofen stereochemistry: Double-the-trouble?

Racemic ibuprofen is an important NSAID used in the treatment of pain and i nflammation in a variety of musculoskeletal and rheumatic disorders. The me tabolism of ibuprofen, and that of a number of the related 2-arylpropionic acid NSAIDs, involves chiral inversion of the relatively inactive X-enantio mers to their active S-antipodes, together with other potentially stereosel ective conjugative and oxidative pathways. Enantiospecific analytical metho dology suitable for the determination of both the drug and its metabolites is essential in order to evaluate the significance of stereoselectivity bot h in terms of drug action and disposition. Recent investigations have also indicated that the R-enantiomers of these agents may not be totally devoid of useful biological activity, that the formation of acyl-coenzyme A deriva tives results in interactions with lipid biochemistry, and has provided new insights into the disposition of these drugs in man. Ibuprofen represents a classical example of a drug where stereochemical considerations are essen tial for an understanding of its biological properties.