Single enantiomer drugs: should they be developed?

Biological interactions are stereoselective; thus the interactions of drugs with corresponding biological targets must also be stereoselective. However, many drugs used today are racemic mixtures. For example, approximately 25% or 1 in 4 marketed drugs are mixtures of agents (racemates) rather than single chemical entities (enantiomers). One of these enantiomers can be inactive or even counterproductive to the therapeutic use of the drug: either by reducing the efficacy of the active enantiomer or by causing unnecessary tolerability problems or even toxicity through differential pharmacodynamics. The presence of a therapeutically inactive or counterproductive enantiomer can also complicate the pharmacokinetics of the active enantiomer and the interpretation of the therapeutic drug monitoring (e.g., plasma levels) if the assay is not capable of separately quantitating the two enantiomers. This article reviews the history of stereoisomers and the relevant pharmacological principles, then discusses recent changes in rules governing drug approval and the potential advantages to the patient and the manufacturer of developing single enantiomers.