Review article: understanding the pharmacodynamic and pharmacokinetic differences between proton pump inhibitors – focus on pKa and metabolism

Proton pump inhibitors (PPIs) have been shown to be clinically more effective than other antisecretory agents, including H₂-receptor antagonists, in the treatment of acid-related disorders and are recognized as the treatment of choice in gastro-oesophageal reflux disease (GERD).¹

Five PPIs are currently available in the United States: omeprazole, its S-enantiomer esomeprazole, lansoprazole, pantoprazole and rabeprazole. PPIs are effective in suppressing gastric acid, controlling GERD symptoms and healing erosive oesophagitis and ulcers.

There are differences in pharmacodynamic and pharmacokinetic profiles among PPIs, including the onset of gastric acid suppression, routes of metabolism and specific drug–drug interactions. Some of these differences may affect the clinical utility of these agents, at least in certain clinical settings. Using rabeprazole as an example, this article investigates some of the pharmacodynamic and pharmacokinetic properties among PPIs, specifically pKa, routes of metabolism and the effect of food.

In addition to reviewing the results of studies with PPIs concerning these factors, this article will define and more fully describe these measures/mechanisms to further our understanding of their impact. Finally, this article discusses the potential clinical significance of these pharmacological properties.