Lansoprazole (lansoprazole)

Lansoprazole, commonly referred to as an acid- or proton-pump inhibitor, is a gastric antisecretory agent.

Lansoprazole is a substituted benzimidazole gastric antisecretory agent. Lansoprazole is structurally and pharmacologically related to dexlansoprazole, esomeprazole, omeprazole, pantoprazole, and rabeprazole; lansoprazole differs structurally from omeprazole by the presence of a trifluoroethoxy group in position 4 of the pyridine ring and the absence of methyl and methoxy groups on the pyridine and benzimidazole rings, respectively. The drugs are chemically and pharmacologically unrelated to H2-receptor antagonists, antimuscarinics, or prostaglandin analogs.

Lansoprazole is a racemic mixture of R- and S-isomers. Both isomers inhibit hydrogen/potassium adenosine triphosphatase (H+K+-exchanging ATPase), but plasma clearance of the R-isomer (dexlansoprazole) is slower than that of the S-isomer; following oral administration of racemic lansoprazole, plasma concentrations of the R-isomer are markedly higher than those of the S-isomer.

Lansoprazole binds to H+K+-exchanging ATPase in gastric parietal cells; inactivation of this enzyme system (also known as the proton, hydrogen, or acid pump) blocks the final step in the secretion of hydrochloric acid by these cells. Therefore, gastric antisecretory agents such as lansoprazole are commonly referred to as acid- or proton-pump inhibitors. Lansoprazole, a weak base, does not directly inhibit this enzyme system, but instead, it concentrates under the acid conditions of the parietal cell secretory canaliculi, where the drug undergoes rearrangement to active sulfenamide metabolites; these active metabolites then react with the sulfhydryl groups of H+K+-exchanging ATPase inactivating the proton pump.

Because the sulfenamide metabolites form an irreversible covalent bond to H+K+-exchanging ATPase, acid secretion is inhibited until additional enzyme is synthesized, resulting in a prolonged duration of action.

Lansoprazole inhibits basal and stimulated gastric acid secretion; in addition, because the drug inhibits the final step in the secretory pathway, it inhibits such secretion regardless of the stimulus. The degree of inhibition of gastric acid secretion is related to the dose and duration of therapy, but lansoprazole is a more potent inhibitor of such secretion than are H2-receptor antagonists. Following oral administration of 15 or 30 mg of lansoprazole, inhibition of gastric acid secretion is apparent within 2-3 or 1-2 hours, respectively.

After multiple daily doses, increased gastric pH is apparent within 1 hour of administration of 30 mg of lansoprazole and within 1-2 hours after administration of 15 mg of the drug.

Although lansoprazole has a short terminal plasma half-life, the drug has a long duration of action (secondary to the prolonged presence of active lansoprazole metabolites within the parietal cell where they bind to H+K+-exchanging ATPase). Following continuous oral administration of 15 or 30 mg of lansoprazole, the percent of time during a 24-hour period that the gastric pH exceeds 4 is 49 or 66%, respectively. Inhibition of basal gastric secretion is 71% after an initial oral dose of 30 mg and 80% or greater after 7 days of oral administration of 30 mg of lansoprazole daily.

Stimulated gastric secretion initially is reduced 81% after an oral dose of 30 mg of lansoprazole and gastric secretion is reduced 88% after 7 days of oral administration of 30 mg of lansoprazole daily. Oral administration of lansoprazole 60 mg produced almost complete inhibition of gastric acid secretion in some patients. Following discontinuance of lansoprazole therapy, gastric acid secretion returns to baseline over a 2- to 4-day period, without rebound gastric acidity.

The degree of inhibition of gastric acid secretion is similar following oral or IV administration (a parenteral formulation no longer is commercially available in the US) of lansoprazole 30 mg daily for 7 days in healthy individuals. Following oral or IV administration of the drug, the percent of time during a 24-hour period that the gastric pH exceeds 4 is about 67 or 71%, respectively, after an initial dose of 30 mg and about 78 or 80%, respectively, after 5 days of administration of lansoprazole 30 mg daily in healthy individuals.

Lansoprazole increases plasma gastrin concentrations; this increase occurs in response to a negative feedback mechanism resulting from decreased gastric acid secretion. Although a single oral dose of 30 mg of lansoprazole did not affect serum gastrin levels in healthy adults, patients with gastric ulcer receiving 30-60 mg of lansoprazole once daily for 2 months developed a 50-100% increase from baseline in median fasting serum gastrin concentration; however, median serum gastrin levels remained within the normal range. Serum gastrin concentrations reach a plateau within 2 months of lansoprazole therapy and return to pretreatment values within 1-12 weeks after discontinuing therapy with the drug.

Although marked hypergastrinemia with subsequent enterochromaffin-like (ECL) cell proliferation and carcinoid lesions have been observed in animal studies, no evidence of similar ECL cell effects were observed in patients receiving the drug for periods of at least one year. Longer-term study and experience are needed to rule out the possibility of an increased risk of gastric tumors in patients receiving prolonged lansoprazole therapy.

Lansoprazole also decreases pepsin secretion and activity and increases serum pepsinogen; however, these effects are not as pronounced as the drug's inhibition of gastric acid secretion. Suppression of pepsin activity appears to be secondary to increased gastric pH, as conversion of the inactive precursor pepsinogen to pepsin requires an acidic gastric milieu. Pepsin output is inhibited in healthy adults receiving 30 mg of lansoprazole daily for 7 days in the morning or evening by 42-58 or 67-88%, respectively.

When the dose is increased to 60 mg daily, no additional inhibition of pepsin secretion is observed. Pepsin activity also is inhibited by lansoprazole 30 mg daily administered in the morning or evening by 23 or 35%, respectively. Lansoprazole also substantially prolongs gastric emptying of digestible solids, but does not appear to affect lower esophageal sphincter pressure.

Lansoprazole can suppress Helicobacter pylori (formerly Campylobacter pylori or C. pyloridis) in patients with gastric or duodenal ulcers infected with the organism. Combined therapy with lansoprazole and one or more appropriate anti-infectives (e.g., amoxicillin, clarithromycin) can effectively eradicate H. pylori gastric infection.

Lansoprazole is extensively metabolized in the liver. Cytochrome P-450 (CYP) isoenzymes 2C19 and 3A4 are involved in the metabolism of the drug. Following single-dose oral administration of lansoprazole, approximately one-third of the administered dose is eliminated in urine and two-thirds in feces; unchanged drug is not recovered in urine.

Therapy with proton-pump inhibitors, particularly in high dosages and/or for prolonged periods of time, may be associated with an increased risk of osteoporosis-related fractures of the hip, wrist, or spine. The mechanism by which these drugs may increase risk of such fractures has not been elucidated but may involve decreased insoluble calcium absorption secondary to increased gastric pH.

Lansoprazole is used orally for the short-term treatment and symptomatic relief of active duodenal and benign gastric ulcer and as maintenance therapy following healing of duodenal ulcers. Lansoprazole also is used orally in combination with amoxicillin (dual therapy) or with clarithromycin and amoxicillin (triple therapy) for the treatment of Helicobacter pylori infection and duodenal ulcer disease. Lansoprazole also has been used in other multiple-drug regimens+ for the treatment of H. pylori infection associated with peptic ulcer disease.

Lansoprazole also is used orally for the treatment of nonsteroidal anti-inflammatory agent (NSAIA)-induced gastric ulcers in patients who continue NSAIA use, and for the prevention of NSAIA-induced gastric ulcers in patients with a documented history of gastric ulcer who require the use of an NSAIA. Oral lansoprazole also is used for short-term treatment and symptomatic relief of gastroesophageal reflux disease (e.g., erosive esophagitis), as maintenance therapy following healing of erosive esophagitis to reduce its recurrence and in the long-term treatment of pathologic GI hypersecretory conditions. Lansoprazole is used orally as self-medication for short-term treatment of frequent heartburn.

Generic name: lansoprazole
Pronunciation: (lan-SO-pruh-zole)

The following indications are listed for Lansoprazole:

• Duodenal Ulcer
• Duodenal Ulcer Due To H. Pylori
• Erosive Esophagitis
• Gastric Hypersecretion With Systemic Mastocytosis
• Gastric Ulcer
• Gastroesophageal Reflux Disease
• Heartburn
• Helicobacter Pylori Gastritis
• Maintenance Of Healing Duodenal Ulcer
• Maintenance Of Healing Erosive Esophagitis
• Nsaid-Induced Gastric Ulcer
• Pathological Gastric Acid Hypersecretory Condition
• Prevention Of Nsaid-Induced Gastric Ulcer
• Zollinger-Ellison Syndrome

Also known as: Adenomatosis Partial Multiple Endocrine, Brash, Campylobacter Gastritis, Du Due To H. Pylori, Duodenal Ulcer Due To Campylobacter Pylori, Duodenal Ulcer Due To Helicobacter Pylori, Gastric Acid Hypersecretory Conditions Due To Disease, Gastro-Esophageal Reflux, Ge Reflux Disease, H. Pylori Gastritis, Maintenance Of Healing Du, Nonsteroidal Anti-Inflammatory Agent-Induced Gastric Ulcer, Nsaid Drug-Induced Gastric Ulcer, Nsaid-Induced Gastric Ulcer Prophylaxis, Pancreatic Ulcerogenic Tumor Syndrome, Pathological Gastric Acid Hypersecretory States, Pathological Hypersecretion State, Pathological Hypersecretory Condition, Pyrosis, Systemic Mast Cell Disease With Gastric Hypersecretion, Z-E Syndrome.

No ICD codes are available for this drug.