Mechanism of Action of Lansoprazole
Lansoprazole works by specifically inhibiting the hydrogen-potassium adenosine triphosphatase (H+/K+-ATPase) enzyme system at the secretory surface of gastric parietal cells, which is the final step in gastric acid production.
Primary Mechanism
Lansoprazole belongs to the class of proton pump inhibitors (PPIs) that act by:
- Irreversibly binding to the H+/K+-ATPase enzyme (also known as the gastric acid pump) located on the secretory surface of gastric parietal cells 1
- Blocking the final step of acid production in the stomach by inhibiting this proton pump 1
- This inhibition is dose-related and leads to suppression of both basal and stimulated gastric acid secretion regardless of the stimulus 1
Pharmacodynamic Effects
When administered orally, lansoprazole produces several measurable effects:
- Significantly decreases basal acid output
- Increases mean gastric pH and the percentage of time gastric pH is greater than 3 and 4
- Reduces meal-stimulated gastric acid output and secretion volume
- Inhibits pentagastrin-stimulated acid output 1
Onset and Duration of Action
- After initial dosing, increased gastric pH is seen within 1-2 hours with 30 mg of lansoprazole and 2-3 hours with 15 mg 1
- With multiple daily dosing, increased gastric pH occurs within the first hour post-dosing with 30 mg and within 1-2 hours with 15 mg 1
- The inhibition of gastric acid secretion gradually returns to normal over 2-4 days after multiple doses, with no rebound gastric acidity 1
Pharmacokinetic Considerations
- Lansoprazole is rapidly absorbed from its gastric acid-resistant formulation 2
- It is extensively metabolized in the liver by cytochrome P450 enzymes (CYP3A4 and CYP2C18) 2
- The mean plasma elimination half-life is between 1.3 and 2.1 hours in healthy volunteers 2
Distinguishing Features from Other Acid Suppressants
Unlike histamine H2-receptor antagonists:
- Lansoprazole does not exhibit anticholinergic or histamine type-2 antagonist activity 1
- It acts at the final common pathway of acid secretion rather than blocking one specific stimulus 3
Unlike potassium-competitive acid blockers (P-CABs):
- PPIs like lansoprazole require activation in an acidic environment and irreversibly bind to the proton pump
- P-CABs have a different mechanism, binding reversibly to the proton pump without requiring activation 4
Clinical Implications of Mechanism
- Optimal efficacy requires proper timing of administration (30 minutes before meals) to ensure the drug reaches peak plasma concentration when proton pumps are most active 5
- Morning dosing generally provides better daytime control of gastric acidity 5
- The acid suppression may enhance the effect of antimicrobials in eradicating Helicobacter pylori 1
Lansoprazole's mechanism of action makes it effective for various acid-related disorders, including peptic ulcer disease, gastroesophageal reflux disease, and hypersecretory conditions like Zollinger-Ellison syndrome.