Objective: To review the comparative efficacy and safety of the proton pump inhibitors (PPIs)--omeprazole, lansoprazole, pantoprazole, and rabeprazole--in the management of acid-related diseases.

Data sources: English-language journal articles retrieved from a MEDLINE search from 1990 to the present using these index terms: proton pump inhibitors, omeprazole, lansoprazole, pantoprazole, rebeprazole, and each of the acid-related diseases.

Study selection: Clinical trials and pertinent review articles that discussed the pharmacology, pharmacokinetics, efficacy, and safety of PPIs in the management of acid-related disease.

Data extraction: By the authors.

Data synthesis: PPIs are substituted benzimidazoles that inhibit gastric acid secretion by covalently binding to the proton pump (H+/K+ ATPase). All undergo extensive hepatic metabolism and conjugation. The four agents differ in their metabolism by and effects on specific hepatic enzymes and thus in their ability to interact with other medications. PPIs are important agents used for eradicating Helicobacter pylori, in treating peptic ulcer disease, gastroesophageal reflux disease, Zollinger-Ellison syndrome, and upper gastrointestinal bleeding, and for preventing acid aspiration. Short-term side effects of the four agents are similar. The long-term safety of pantoprazole and rabeprazole appears similar to that of omeprazole and lansoprazole. Pantoprazole, which is in the final stages of approval for marketing in the United States, will be available in both an oral and injectable formulation.

Conclusion: Based on superior efficacy profiles, PPIs are the drugs of choice in managing patients with peptic ulcer disease, gastroesophageal reflux disease, and Zollinger-Ellison syndrome. The decision to select one PPI versus another is most likely to be based on the agents' acquisition costs, formulations, FDA-labeled indications, and overall safety profiles. Intravenous or parenteral pantoprazole may become the preferred antisecretory agent for patients unable to take oral medications (e.g., critically ill patients and those with Zollinger-Ellison syndrome).