Testa B, Reist M, Carrupt P A
Institut de chimie thérapeutique, BEP, Université de Lausanne, CH-1015 Lausanne-Dorigny.
Ann Pharm Fr. 2000 Jul;58(4):239-46.
The two enantiomers of a chiral drug may have vastly different pharmacodynamic and pharmacokinetic properties. As a result, the research and development of chiral drugs raises specific problems some of which are discussed here. Thus, various pharmacokinetic interactions may involve two enantiomers, as seen for example when one enantiomer inhibits the metabolism of the other and modifies its effects. A different situation occurs when a third compound stereoselectively inhibits the metabolism of one of the two enantiomers. Another problem examined here results from the lack of configurational stability of some chiral drugs, a little known phenomenon whose consequences can be of pharmacological or pharmaceutical significance depending on the rate of the reaction of racemization or epimerisation. In-depth investigations are needed before choosing between a eutomer or a racemate.
手性药物的两种对映体可能具有截然不同的药效学和药代动力学性质。因此,手性药物的研发引发了一些特定问题,本文将讨论其中的一些问题。例如,各种药代动力学相互作用可能涉及两种对映体,就像一种对映体抑制另一种对映体的代谢并改变其效应时那样。当第三种化合物立体选择性地抑制两种对映体之一的代谢时,会出现不同的情况。本文探讨的另一个问题源于一些手性药物构型稳定性的缺乏,这是一个鲜为人知的现象,其后果根据外消旋化或差向异构化反应的速率可能具有药理学或药学意义。在选择优映体或外消旋体之前,需要进行深入研究。