What are the commonly used Proton Pump Inhibitors (PPIs)?

Commonly Used Proton Pump Inhibitors (PPIs)

The commonly used proton pump inhibitors (PPIs) include omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, and dexlansoprazole. 1

Available PPIs and Their Characteristics

• Omeprazole: One of the first PPIs developed, available in both prescription and over-the-counter formulations 1
• Lansoprazole: Has a longer duration of action compared to omeprazole 2
• Pantoprazole: Has less interaction with the cytochrome P-450 system and more predictable bioavailability 2
• Rabeprazole: Displays a slightly more rapid onset of acid inhibition than other PPIs 3
• Esomeprazole: The S-isomer of omeprazole, exhibits somewhat higher potency than other PPIs 3
• Dexlansoprazole: A newer PPI with a dual delayed-release formulation that provides two separate releases of medication 4

Mechanism of Action

• All PPIs irreversibly inhibit the enzyme hydrogen-potassium adenosine triphosphatase (H+/K+-ATPase), also known as the gastric acid pump 4
• PPIs are prodrugs that are converted to their active form in the acidic environment of the parietal cells 1
• Once activated, they bind covalently to the proton pump, blocking the final step of acid production 4

Clinical Applications

• PPIs are the most potent gastric acid-suppressing agents in clinical use 5
• Standard daily doses include:
  • Omeprazole: 20 mg
  • Lansoprazole: 30 mg
  • Pantoprazole: 40 mg
  • Rabeprazole: 20 mg
  • Esomeprazole: 20 mg
  • Dexlansoprazole: 30-60 mg 5, 4

Pharmacokinetic Considerations

• All PPIs are metabolized by the hepatic cytochrome P-450 system, predominantly CYP2C19 1
• Rabeprazole and pantoprazole appear to have the lowest risk for drug interactions 6
• Omeprazole has the highest risk for drug interactions among PPIs 6
• Genetic polymorphisms in CYP2C19 can affect PPI metabolism, particularly for omeprazole, lansoprazole, and pantoprazole, but less so for rabeprazole 1

Relative Potency

• PPIs vary in their relative potency for acid suppression 1
• Comparative potency (equivalent to 20 mg omeprazole):
  • 30 mg lansoprazole = 27 mg omeprazole
  • 40 mg pantoprazole = 9 mg omeprazole
  • 20 mg rabeprazole = 36 mg omeprazole
  • 20 mg esomeprazole = 32 mg omeprazole 1

Emerging Alternatives

• Potassium-competitive acid blockers (P-CABs) are a newer class of antisecretory medications that may provide more potent acid inhibition than PPIs 1
• Examples of P-CABs include vonoprazan, tegoprazan, revaprazan, fexuprazan, linaprazan, zastaprazan, and keverprazan 1
• Unlike PPIs, P-CABs:
  • Are acid-stable (not acid-labile)
  • Are not prodrugs
  • Bind reversibly to the proton pump
  • Have longer half-lives
  • Can be administered independently of mealtimes 1

Clinical Considerations

• PPIs are generally safe but should only be used when there is a reasonable expectation of benefit based on scientific evidence or prior treatment response 1
• Long-term PPI use has been associated with various adverse effects, including nutrient deficiencies, increased risk of infections, bone fractures, and kidney problems 7
• Regular review of ongoing indications for PPI use is recommended 1
• When prescribing PPIs for H. pylori eradication, higher-potency PPIs (esomeprazole or rabeprazole) are recommended at doses of 20-40 mg twice daily 1

PPIs remain cornerstone medications for treating acid-related disorders, but their use should be tailored to specific clinical situations with consideration of their individual pharmacological properties 7.