Review article: The clinical pharmacology of proton pump inhibitors

G. Sachs, J. M. Shin, C. W. Howden

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

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. The relative ease with which these steps occur with different proton pump inhibitors underlies differences in their rates of activation, which in turn influence the location of covalent binding and the stability of inhibition. Slow activation is associated with binding to a cysteine residue involved in proton transport that is located deep in the membrane. However, this is inaccessible to the endogenous reducing agents responsible for restoring H+/K+-ATPase activity, favouring a longer duration of gastric acid inhibition. Pantoprazole and tenatoprazole, a novel proton pump inhibitor which has an imidazopyridine ring in place of the benzimidazole moiety found in other proton pump inhibitors, are activated more slowly than other proton pump inhibitors but their inhibition is resistant to reversal. In addition, tenatoprazole has a greatly extended plasma half-life in comparison with all other proton pump inhibitors. The chemical and pharmacological characteristics of tenatoprazole give it theoretical advantages over benzimidazole-based proton pump inhibitors that should translate into improved acid control, particularly during the night.

Original languageEnglish (US)
Pages (from-to)2-8
Number of pages7
JournalAlimentary Pharmacology and Therapeutics
Volume23
Issue numberSUPPL. 2
DOIs
StatePublished - Jun 1 2006

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Clinical Pharmacology
Proton Pump Inhibitors
Cysteine
H(+)-K(+)-Exchanging ATPase
Proton Pumps
Acids
Proton-Translocating ATPases
Gastric Acid
Reducing Agents
Half-Life
Protons
Pharmacology
Membranes

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

Cite this

Review article : The clinical pharmacology of proton pump inhibitors. / Sachs, G.; Shin, J. M.; Howden, C. W.

In: Alimentary Pharmacology and Therapeutics, Vol. 23, No. SUPPL. 2, 01.06.2006, p. 2-8.

Research output: Contribution to journalArticle

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