Stereoselective Pharmacodynamics and Pharmacokinetics of Proton Pump Inhibitors

Author(s): Zhi-Cheng Yang, Feng Yu, Yong-Qing Wang, Ji-Fu Wei

Journal Name: Current Drug Metabolism

Volume 17 , Issue 7 , 2016

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Abstract:

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Chirality, pharmacodynamics, pharmacogenomics, pharmacokinetic, proton pump inhibitors (PPIs), stereoselective.

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Article Details

VOLUME: 17
ISSUE: 7
Year: 2016
Published on: 14 July, 2016
Page: [692 - 702]
Pages: 11
DOI: 10.2174/1389200217666160322143857
Price: $65

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