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Stereoselective pharmacokinetics and chiral inversions of some chiral hy-droxy group drugs.
Current Pharmaceutical Biotechnology ( IF 2.8 ) Pub Date : 2020-11-30 , DOI: 10.2174/1389201021666200727144053
Fuxin Chen 1 , Qiaoxiu Bai 1 , Qingfeng Wang 1 , Suying Chen 1 , Xiaoxian Ma 1 , Changlong Cai 2 , Danni Wang 3 , Ahsan Waqas 1 , Pin Gong 3
Affiliation  

Background: Chiral safety, especially chiral drug inversion in vivo, is the top priority of current scientific research. Medicine researchers and pharmacists often ignore that one enantiomer will be converted or partially converted to another enantiomer when it is ingested in vivo. So that, in the context that more than 50% of the listed drugs are chiral drugs, it is necessary and important to pay attention to the inversion of chiral drugs.

Methods: The metabolic and stereoselective pharmacokinetic characteristics of seven chiral drugs with one chiral center in the hydroxy group were reviewed in vivo and in vitro including the possible chiral inversion of each drug enantiomer. These seven drugs include (S)-Mandelic acid, RS-8359, Tramadol, Venlafaxine, Carvedilol, Fluoxetine and Metoprolol.

Results: The differences in stereoselective pharmacokinetics could be found for all the seven chiral drugs, since R and S isomers often exhibit different PK and PD properties. However, not every drug has shown the properties of one direction or two direction chiral inversion. For chiral hydroxyl group drugs, the redox enzyme system may be one of the key factors for chiral inversion in vivo.

Conclusion: In vitro and in vivo chiral inversion is a very complex problem and may occur during every process of ADME. Nowadays, research on chiral metabolism in the liver has the most attention, while neglecting the chiral transformation of other processes. Our review may provide the basis for the drug R&D and the safety of drugs in clinical therapy.



中文翻译:

某些手性羟基基团药物的立体选择性药代动力学和手性反转。

背景:手性安全性,特别是体内手性药物倒置,是当前科学研究的重中之重。医学研究人员和药剂师通常忽略了一种对映异构体在体内摄入后会转化为或部分转化为另一种对映异构体的情况。因此,在列出的药物超过50%是手性药物的情况下,必须注意手性药物的倒置,这是必要且重要的。

方法:在体内和体外研究了7种在羟基上具有一个手性中心的手性药物的代谢和立体选择性药代动力学特征,包括每种药物对映体的可能手性转化。这七种药物包括(S)-扁桃酸,RS-8359,曲马多,文拉法辛,卡维地洛,氟西汀和美托洛尔。

结果:由于R和S异构体经常表现出不同的PK和PD特性,因此对所有7种手性药物而言,立体选择性药代动力学均存在差异。但是,并非每种药物都显示出一个方向或两个方向的手性反转特性。对于手性羟基药物,氧化还原酶系统可能是体内手性转化的关键因素之一。

结论:体外和体内手性反转是一个非常复杂的问题,可能在ADME的每个过程中发生。如今,对肝脏中手性代谢的研究最为关注,而忽略了其他过程的手性转化。我们的审查可能为药物研发和临床治疗中药物的安全性提供基础。

更新日期:2020-12-23
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