Today, preclinical development of new chemical entities must take into account, at very early stages, the issue of whether the molecule possesses any chiral centers. If so, the enantiomers should be resolved, and their efficacy, toxicity, and safety should be assessed. The results of these studies will help determine whether to develop an individual enantiomer or the racemate. The decision to develop a racemate or an enantiomer should be made only after a thorough understanding of the pharmacological, toxicological, and pharmacokinetic properties of the substance. Although not all-inclusive, the following examples illustrate typical situations in which a racemate might be developed (23):

The enantiomers have been shown to have pharmacological and toxicologi-

cal profiles similar to the racemate. The enantiomers are rapidly interconverted in vitro and/or in vivo so that administration of a single enantiomer offers no advantage. One enantiomer of the racemate is shown to be pharmacologically inactive, and the racemate is demonstrated to be safe and effective. Synthesis or isolation of the preferred enantiomer is not practical. Individual enantiomers exhibit different pharmacological profiles, and the racemate produces a superior therapeutic effect relative to either enan-tiomer alone.

The decision to market one enantiomer or the racemate should be made on a case-by-case basis after considering all available data.

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