European Journal of Clinical Pharmacology

, Volume 64, Issue 10, pp 935–951

Proton pump inhibitors: an update of their clinical use and pharmacokinetics

Review Article

Abstract

Background

Proton pump inhibitors (PPIs) represent drugs of first choice for treating peptic ulcer, Helicobacter pylori infection, gastrooesophageal reflux disease, nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal lesions (complications), and Zollinger-Ellison syndrome.

Results

The available agents (omeprazole/esomeprazole, lansoprazole, pantoprazole, and rabeprazole) differ somewhat in their pharmacokinetic properties (e.g., time-/dose-dependent bioavailability, metabolic pattern, interaction potential, genetic variability). For all PPIs, there is a clear relationship between drug exposure (area under the plasma concentration/time curve) and the pharmacodynamic response (inhibition of acid secretion). Furthermore, clinical outcome (e.g., healing and eradication rates) depends on maintaining intragastric pH values above certain threshold levels. Thus, any changes in drug disposition will subsequently be translated directly into clinical efficiency so that extensive metabolizers of CYP2C19 will demonstrate a higher rate of therapeutic nonresponse.

Conclusions

This update of pharmacokinetic, pharmacodynamic, and clinical data will provide the necessary guide by which to select between the various PPIs that differ—based on pharmacodynamic assessments—in their relative potencies (e.g., higher doses are needed for pantoprazole and lansoprazole compared with rabeprazole). Despite their well-documented clinical efficacy and safety, there is still a certain number of patients who are refractory to treatment with PPIs (nonresponder), which will leave sufficient space for future drug development and clinical research.

Keywords

Proton pump inhibitors Pharmacokinetics Pharmacodynamics Peptic ulcer Reflux disease Helicobacter pylori infection 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Dr. Margarete Fischer-Bosch-Institut für Klinische PharmakologieStuttgartGermany
  2. 2.University of TuebingenTuebingenGermany
  3. 3.Department of Pharmacy of Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China

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