Clinical Use of Proton Pump Inhibitors in Gastrointestinal Diseases

Rew, Jong Sun

Abstract

The development and introduction into clinical practice of proton pump inhibitors (PPIs) have influenced the management of acid-peptic disorders dramatically. PPIs inhibit the gastric hydrogen/potassium adenosine triphosphatase selectively and irreversibly which is the final step in acid secretion. PPIs are currently the most effective form of therapy in acid-peptic diseases. All PPIs are potent, effective and generally safe, but little different in equivalent doses. PPIs undergo hepatic metabolism by cytochrome P450 (CYP) system. Polymorphism of CYP2C19 influences the pharmacokinetics and pharmacodynamics of PPIs. Doses and dosing schemes of PPIs based on CYP2C19 genotype status is expected to increase the efficacy in clinical outcome. The major indication of PPIs are acid-related diseases such as peptic ulcers and their complications, gastroesophageal reflux diseases, Zollinger-Ellison syndrome and eradication of Helicobacter pylori with antibiotics and dyspepsia. The potency and cost-effectiveness of PPIs have extended their clinical uses. However, their widespread and long-term use may limit the therapeutic benefit between efficacy and clinical problems such as acid rebound hypersecretion, enhanced oxyntic gastritis, problems with carcinoids in rodents and long-term concern for gastric cancer development. Further studies are needed to minimize the side effects and to maximize the therapeutic effects of PPIs.