Description

Rabeprazole is a synthetic, substituted benzimidazole that belongs to the class of medications known as proton pump inhibitors (PPIs). Like other PPIs, it works by reducing the amount of acid produced in the stomach. Rabeprazole is supplied as an enteric-coated tablet or capsule to protect the drug from degradation by stomach acid, ensuring it reaches the small intestine for absorption.

Indications

Rabeprazole is used for the treatment of various acid-related conditions. Its indications include:

• Gastroesophageal Reflux Disease (GERD): It is used for the short-term treatment of symptoms of GERD and for the healing of erosive or ulcerative GERD. It is also used for the long-term maintenance of healing.
• Duodenal Ulcers: It is used for the treatment and healing of active duodenal ulcers.

• Helicobacter pylori (H. pylori) eradication: Rabeprazole is a key component of multi-drug regimens, typically with two antibiotics, to eradicate H. pylori infection, which is a major cause of peptic ulcers.

• Zollinger-Ellison Syndrome: It is used for the long-term management of this rare hypersecretory condition.

Mechanism of Action

Rabeprazole’s mechanism of action is based on its ability to inhibit the enzyme that pumps acid into the stomach. It works similarly to other PPIs but with a few key differences in its activation and metabolism.

1. Prodrug Activation: Rabeprazole is a prodrug, meaning it is inactive until it is activated. After being absorbed from the small intestine, it enters the bloodstream and travels to the acid-secreting parietal cells in the stomach lining.
2. Conversion to Active Form: In the highly acidic secretory canaliculi of these cells, rabeprazole is converted into its active form, a sulfenamide.
3. Irreversible Inhibition: This activated form then forms a permanent, irreversible covalent bond with the H+/K+-ATPase enzyme, also known as the “proton pump.” This pump is the final and most crucial step in the secretion of gastric acid.
4. Cessation of Acid Production: By permanently blocking the proton pump, rabeprazole effectively prevents the production and secretion of gastric acid. This suppression affects both basal (resting) acid secretion and acid secretion stimulated by food or other factors.

A notable feature of rabeprazole is its faster onset of action compared to some other PPIs. It has a higher pKa (a measure of acidity) than omeprazole and lansoprazole, which allows it to concentrate more readily in the acidic environment of the parietal cells, leading to faster activation and a more rapid onset of acid suppression. Additionally, its metabolism is less dependent on certain cytochrome P450 enzymes (like CYP2C19), which can result in more consistent and predictable drug levels across different patient populations.