Albuterol enantiomers: Pre-clinical and clinical value?

Albuterol has been used in the acute treatment of asthma exacerbations for over 25 years. Its cost is low, and delivery can be tailored to allow dose-effect titration. Like other beta-2-adrenergic receptor agonists, it can exist as a racemate of two enantiomers, one active [(R)-albuterol], and one traditionally considered inert [(S)-albuterol]. Basic investigations in airway cells and models from animals and humans have shown that (R)-albuterol, in both racemic and single enantiomer formulations, produces changes consistent with both relaxation of airway smooth muscle cells, and the reduction of inflammation. In contrast, (S)-albuterol typically has produces effects opposite to those of (R)-albuterol, i.e., antagonistic to the beneficial desired effects. Coupled with the fact that (S)-albuterol can persist 12 times longer than (R)-albuterol within the human circulation, findings suggest that paradoxical effects, sometimes seen with chronic racemic albuterol use, are due to (S)-albuterol. A number of clinical studies, to date, have been generally consistent with these findings; however, overwhelming evidence for clinical superiority of the (R)-albuterol single enantiomer over that within racemic albuterol remains to be obtained.