Yang Zhi-Cheng, Yu Feng, Wang Yong-Qing, Wei Ji-Fu
Research Division of Clinical Pharmacology, The first affiliated hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, China, 210029.
Curr Drug Metab. 2016;17(7):692-702.
Proton pump inhibitors (PPIs) are a group of gastric acid suppressing drugs, they work by irreversibly blocking the H+/K+ ATPase. The structure of PPIs is similar. They all have a similar core with a sulphur atom chiral center combined with different substituent groups. In relation to the sulphur atom chiral center, the pharmacodynamics, pharmacokinetics are diverse between the racemates and their stereoisomers. But there are no reviews outlining the stereoselective pharmacodynamics and pharmacokinetics in PPIs. This review aims to compare the differences between the stereoisomers of PPIs in their pharmacodynamics and pharmacokinetics parameters. And exploring the development directions of PPIs at present.
We undertook a search of PubMed databases for PPI research literature including reviews, clinical studies, letters and books, in recent 20 years. The citied papers were high quality, which were carefully screened by authors using standard tools. The data of the pharmacodynamics and pharmacokinetics parameters were selected from the retrieved papers, then making generalization and summary.
Ninety-three papers were included in the review, mainly from East Asia, America and Europe. All these papers involved the reviews of PPIs, the pharmacodynamics studies of PPIs and the pharmacokinetics studies of PPIs. Finally, omeprazole, lansoprazole, pantoprazole, rebeprazole and pantoprazole with their enantiomers were discussed in this paper.
The findings of this review confirm the differences of pharmacodynamics and pharmacokinetics in the racemates and the stereoisomer of PPIs. Providing longer duration, faster time of onset and better nocturnal gastric acid secretion control are the development directions of new generation PPIs. But, due to debate on the necessity and superiority of these new drugs, more validation studies are needed.
质子泵抑制剂（PPIs）是一类胃酸抑制药物，通过不可逆地阻断H+/K+ ATP酶发挥作用。PPIs的结构相似，它们都有一个相似的核心，带有一个硫原子手性中心，并结合不同的取代基。就硫原子手性中心而言，消旋体及其立体异构体之间的药效学和药代动力学存在差异。但目前尚无概述PPIs立体选择性药效学和药代动力学的综述。本综述旨在比较PPIs立体异构体在药效学和药代动力学参数方面的差异，并探索目前PPIs的发展方向。
我们检索了PubMed数据库中近20年的PPI研究文献，包括综述、临床研究、信函和书籍。所引用的论文质量较高，作者使用标准工具进行了仔细筛选。从检索到的论文中选择药效学和药代动力学参数的数据，然后进行归纳和总结。
该综述纳入了93篇论文，主要来自东亚、美洲和欧洲。所有这些论文都涉及PPIs的综述、PPIs的药效学研究和PPIs的药代动力学研究。最后，本文讨论了奥美拉唑、兰索拉唑、泮托拉唑、雷贝拉唑及其对映体。
本综述的结果证实了PPIs消旋体和立体异构体在药效学和药代动力学方面的差异。提供更长的作用持续时间、更快的起效时间和更好的夜间胃酸分泌控制是新一代PPIs的发展方向。但是，由于对这些新药的必要性和优越性存在争议，需要更多的验证研究。
