Esomeprazole (Nexium)

Esomeprazole - Nexium®

Classification:
Gastrointestinal Agents

• Antiulcer Agents
  
  • Proton pump inhibitors (PPIs)

Description: Esomeprazole, the S-isomer of omeprazole, is the first proton pump inhibitor (PPI) synthesized as an optical isomer to become available for clinical use. Esomeprazole was previously known as perprazole in investigational use. Esomeprazole is approved for the healing and maintenance of erosive esophagitis and for the treatment of symptomatic gastroesophageal reflux disease. Esomeprazole is also indicated for use in combination with clarithromycin and amoxicillin to eradicate Helicobacter pylori in patients with active or prior duodenal ulcer disease. When compared to omeprazole, esomeprazole has similar efficacy in the eradication of H. pylori, can maintain intragastric pH > 4.0 for a longer period of time, and has a similar time to sustained resolution of heartburn. Esomeprazole has a greater bioavailability compared to omeprazole, which may contribute to higher healing rates reported in studies of erosive esophagitis. Esomeprazole (Nexium®) capsules were approved by the FDA on February 20, 2001. On November 29, 2004 the FDA approved oral esomeprazole for the prevention of NSAID-associated gastric ulcers; the sNDA for the healing of NSAID-induced gastric ulcers is ‘approvable’. An injectable formulation of esomeprazole (Nexium®) was approved by the FDA on March 31, 2005.

Mechanism of Action: Esomeprazole is a substituted benzimidazole proton-pump inhibitor (PPI) that suppresses gastric acid secretion by inhibiting the gastric (H+, K+)-ATPase enzyme pump. Following activation in an acidic pH, esomeprazole binds irreversibly to the H+/K+ ATPase pump on the secretory surface of the parietal cell membrane. Subsequently, the secretion of hydrogen ions into the gastric lumen is inhibited. Gastric acid pump inhibitors block the final step of gastric acid production, and inhibit both basal and stimulus-induced acid secretion. Delayed-release doses of 20 mg and 40 mg esomeprazole maintained intragastric pH > 4.0 for 12.7 hours and 16.8 hours, respectively. Significant in vitro activity against Helicobacter pylori (H. Pylori) has been demonstrated for esomeprazole. Esomeprazole monotherapy increases the clearance rate of H. pylori; however, eradication does not occur without appropriate antimicrobial therapy. Similar to omeprazole and other PPIs, hypergastrinemia can occur during esomeprazole therapy. Although prolonged hypergastrinemia has been associated with gastric tumors in rats, long-term studies of proton pump inhibitors do not suggest the development of tumors in humans.

Nexium Delayed-Release Capsules(Cap DR Pel 40 mg)

Pharmacokinetics: Esomeprazole is administered orally. Esomeprazole dissolves rapidly in an acidic environment and therefore is formulated as a capsule containing enteric-coated pellets. Multiple dosing at 40 mg/day results in 90% bioavailability versus 64% after a single 40 mg dose. Cmax is reached within 1 - 3.5 hours. The AUC of esomeprazole (the S-isomer) is 80% higher than with omeprazole (both S- and R-isomer) due to decreased clearance and first-pass elimination of the S-isomer. Clinically this allows more esomeprazole to reach the site of action and may contribute to higher efficacy rates. The AUC of a single 40 mg dose of esomeprazole is decreased by 33 - 53% after food intake compared to fasting conditions. Esomeprazole is 97% bound to plasma proteins. Metabolism occurs extensively in the liver to inactive metabolites via CYP2C19 and to a lesser extent by CYP3A4. The plasma elimination half-life of esomeprazole is approximately 1.5 hours. Less than 1% of parent drug is excreted in the urine with the remainder excreted as inactive metabolites in both the urine and feces.