Review article: the clinical pharmacology of proton pump inhibitors

  title={Review article: the clinical pharmacology of proton pump inhibitors},
  author={George Sachs and J. M. Shin and C. W. Howden},
  journal={Alimentary Pharmacology \& Therapeutics},
Proton pump inhibitors inhibit the gastric H+/K+‐ATPase via covalent binding to cysteine residues of the proton pump. All proton pump inhibitors must undergo acid accumulation in the parietal cell through protonation, followed by activation mediated by a second protonation at the active secretory canaliculus of the parietal cell. 

Proton pump inhibitors: actions and reactions.

Proton pump inhibitors are now massively utilized medications worldwide but their H + ,K + -ATPase and non-H + ,K + -ATPase mediated side effects are poorly appreciated

Proton pump inhibitors have largely displaced H-2 receptor antagonists in the treatment of acid peptic disorders and may influence physiology in other ways, such as inducing transepithelial leak.

Proton pump inhibitors

A reversible acid pump antagonist (APAs), currently in clinical trial removes these problems and the APAs are the conceivable future drugs for the treatment of acid-peptic disorders.

Safety of proton pump inhibitor exposure.

The data available on the putative adverse effects of PPI therapy is summarized, and guidelines for clinicians who prescribe these agents are proposed to limit the potential for adverse outcomes in users of these effective therapeutic agents.


The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H + ions into the gastric lumen, making it an ideal target for inhibiting acid secretion.

Predictable prolonged suppression of gastric acidity with a novel proton pump inhibitor, AGN 201904‐Z

Background  AGN 201904‐Z is a new, slowly absorbed, acid‐stable pro‐proton pump inhibitor (pro‐PPI) rapidly converted to omeprazole in the systemic circulation giving a prolonged residence time.

Safe use of proton pump inhibitors in patients with cirrhosis

This work aims to develop practical guidance on the safe use of PPIs in patients with cirrhosis, and to investigate the role of EMT in the development and use of these drugs.

Analysis of Proton Pump Inhibitors in Bulk and In Different Dosage Forms -A Review

This review entails different methods developed for determination of PPIs like UV-Spectroscopy, liquid Chromatography and LC-MS, which are challenging to develop analytical method where in stability of drug is least hampered.

Review article: dual delayed release formulation of dexlansoprazole MR, a novel approach to overcome the limitations of conventional single release proton pump inhibitor therapy

This data indicates that once‐daily dosing of proton pump inhibitors is a viable treatment option for acid‐related disorders and their use in clinical practice is likely to be safe and effective.

Mechanisms of proton pump inhibitor‐induced hypomagnesemia

It is argued that the increase of the luminal pH during PPI treatment may contribute to several of these mechanisms, and it is proposed that targeting the gut microbiome using dietary intervention might be a promising treatment strategy to restore hypomagnesemia in PPI users.



Review article: immediate‐release proton‐pump inhibitor therapy – potential advantages

  • C. Howden
  • Medicine, Biology
    Alimentary pharmacology & therapeutics
  • 2005
The absorption of most oral proton‐pump inhibitors is delayed by the enteric coating required to protect the acid‐labile proton‐pump inhibitor from degradation in the stomach and, as a result,

Physiology of the Parietal Cell and Therapeutic Implications

  • G. Sachs
  • Medicine, Biology
  • 2003
These agents are important in the management of duodenal ulcers, nonsteroidal antiinflammatory drug‐induced Ulcers, gastroesophageal reflux disease, and dyspepsia, but basic pharmacokinetic and pharmacodynamic differences among them may affect clinical utility.

Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors.

Proton pump inhibitors, drugs that are widely used for treatment of acid related diseases, are either substituted pyridylmethylsulfinyl benzimidazole or imidazopyridine derivatives, and values predict their relative acid stability and thus the rate of reaction with cysteines of the active proton pump at the pH of the secreting parietal cell are obtained.

Restoration of acid secretion following treatment with proton pump inhibitors.

Recovery of acid secretion following inhibition by all PPIs, other than pantoprazole, may depend on both protein turnover and reversal of the inhibitory disulfide bond.

Tenatoprazole, a novel proton pump inhibitor with a prolonged plasma half‐life: effects on intragastric pH and comparison with esomeprazole in healthy volunteers

Tenatoprazole is a novel proton pump inhibitor with a seven‐fold longer plasma half‐life that controls gastric acidity better during the day than at night, when nocturnal acid breakthrough can occur.

Improving on PPI-based therapy of GORD.

  • G. Sachs
  • Biology, Medicine
    European journal of gastroenterology & hepatology
  • 2001
An extension of PPI plasma half-lives is an obvious goal, possibly via exploitation of probable differences in the metabolism of the two enantiomers present in current PPI formulations: e.g., clinical data on the S-enantiomer of omeprazole suggest some improvement in acid control.