CHIRALITY AND NONSTEROIDAL ANTIINFLAMMATORY DRUGS

The nonsteroidal anti-inflammatory drugs (NSAIDs) are of significant c linical importance and include congeners of many chemical classes, som e of which incorporate an asymmetric or chiral carbon atom. With very few exceptions, chiral NSAIDs have bi:en marketed for clinical use as racemates. However, it is apparent that differences, sometimes major, exist between enantiomers in terms of their pharmacological and toxico logical properties. With regard to the ability of chiral NSAIDs to inh ibit cyclo-oxygenase, their chief mechanism of action, major or exclus ive activity is confined to enantiomers of the S-stereoconfiguration. Accordingly, it is questionable whether the R-antipodes should be incl uded in the final drug product for use in the clinic. In addition to d ifferences between enantiomers in terms of their pharmacodynamic prope rties, pharmacokinetic differences are possible for chiral NSAID isome rs, and these may modulate preexisting enantioselectivities at the sit e of action of such compounds. As a consequence. a considerably simple r pharmacological profile is likely to result from the use of single e nantiomers versus racemic mixtures.