The issue of drug chirality is now a major theme in the design and development of new drugs,
underpinned by a new understanding of the role of molecular recognition in many pharmacologically relevant
events. In general, three methods are used for the production of a chiral drug: the chiral pool, separation of
racemates, and asymmetric synthesis. Although the use of chiral drugs predates modern medicine, only since the
1980’s has there been a significant increase in the development of chiral pharmaceutical drugs. The thalidomide
tragedy increased awareness of stereochemistry in the action of drugs, and as a result the number of drugs
administered as racemic compounds has steadily decreased. In 2001, more than 70% of the new chiral drugs
approved were single enantiomers. Approximately 1 in 4 therapeutic agents are marked as racemic mixtures, the
individual enantiomers of which frequently differ in both their pharmacodynamic and pharmacokinetic profiles.
The use of racemates has become the subject of considerable discussion in recent years, and an area of concern
for both the pharmaceutical industry and regulatory authorities. Pharmaceutical companies are required to justify
each decision to manufacture a racemic drug in preference to its homochiral version. Moreover, the use of single
enantiomers has a number of potential clinical advantages, including an improved therapeutic/pharmacological
profile, a reduction in complex drug interactions, and simplified pharmacokinetics. In a number of instances
stereochemical considerations have contributed to an understanding of the pharmacological effects observed of a
drug administered as a racemate. However, relatively little is known of the influence of patient factors (e.g.
disease state, age, gender and genetics) on drug enantiomer disposition and action in man. Examples may also be
cited where the use of a single enantiomer, non-racemic mixtures and racemates of currently used agents may
offer clinical advantages. The issues associated with drug chirality are complex and depend upon the relative
merits of the individual agent. In the future it is likely that a number of existing racemates will be re-marketed as
single enantiomer products with potentially improved clinical profiles and possible novel therapeutic indications.
