Hutt A J, Tan S C
Department of Pharmacy, King's College London, England.
Drugs. 1996;52 Suppl 5:1-12. doi: 10.2165/00003495-199600525-00003.
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. 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 observed pharmacological effects 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 enantiomers, nonracemic 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.
大约四分之一的治疗药物被标记为外消旋混合物，其各个对映体在药效学和药代动力学方面常常存在差异。近年来，外消旋体的使用已成为大量讨论的主题，也是制药行业和监管机构关注的领域。使用单一异构体具有许多潜在的临床优势，包括改善治疗/药理学特性、减少复杂的药物相互作用以及简化药代动力学。在许多情况下，立体化学因素有助于理解作为外消旋体给药的药物所观察到的药理作用。然而，关于患者因素（如疾病状态、年龄、性别和遗传学）对人体药物对映体处置和作用的影响，人们了解得相对较少。也可以列举一些例子，说明使用单一异构体、非外消旋混合物以及现有药物的外消旋体可能具有临床优势。与药物手性相关的问题很复杂，取决于各个药物的相对优点。未来，许多现有的外消旋体可能会作为单一异构体产品重新上市，其临床特性可能得到改善，并可能有新的治疗适应症。
