indication

For the treatment of acid-reflux disorders (GERD), peptic ulcer disease, H. pylori eradication, and prevention of gastroinetestinal bleeds with NSAID use.

pharmacology

Lansoprazole, an acid proton-pump inhibitor similar to omeprazole, is used as an untiulcer drug in the treatment and maintenance of healing of duodenal or gastric ulcers, erosive and reflux esophagitis, NSAID-induced ulcer, Zollinger-Ellison syndrome, and Barrett's esophagus. Lansoprozole is active against Helicobacter pylori. The plasma elimination half-life of lansoprazole does not reflect its duration of suppression of gastric acid secretion. Thus, the plasma elimination half-life is less than two hours, while the acid inhibitory effect lasts more than 24 hours.

mechanism of action

Lansoprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that do not exhibit anticholinergic or histamine H₂-receptor antagonist properties, but rather suppress gastric acid secretion by specific inhibition of the (H⁺,K⁺)-ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the parietal cell, Lansoprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated gastric acid secretion irrespective of the stimulus.

toxicity

Symptoms of overdose include abdominal pain, nausea and diarrhea.

biotransformation

Hepatic. Two metabolites have been identified in measurable quantities in plasma (the hydroxylated sulfinyl and sulfone derivatives of lansoprazole). These metabolites have very little or no antisecretory activity. Lansoprazole is thought to be transformed into two active species which inhibit acid secretion by (H⁺,K⁺)-ATPase within the parietal cell canaliculus, but are not present in the systemic circulation.

absorption

The absorption of lansoprazole is rapid, with mean C_max occurring approximately 1.7 hours after oral dosing, and relatively complete with absolute bioavailability over 80%.

half life

1.5 (± 1.0) hours

route of elimination

Following single-dose oral administration of PREVACID, virtually no unchanged lansoprazole was excreted in the urine. In one study, after a single oral dose of 14C-lansoprazole, approximately one-third of the administered radiation was excreted in the urine and two-thirds was recovered in the feces. This implies a significant biliary excretion of the lansoprazole metabolites.

drug interactions

Atazanavir: This gastric pH modifier decreases the levels/effects of atazanavir

Cefditoren: Proton pump inhibitors such as lansoprazole may decrease the serum concentration of cefditoren. If possible, avoid use of cefditoren with proton pump inhibitors (PPIs). Consider alternative methods to minimize/control acid reflux (eg, diet modification) or alternative antimicrobial therapy if use of PPIs can not be avoided.

Clopidogrel: Lansoprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Due to the possible risk for impaired clopidogrel effectiveness with this combination, clinicians should carefully consider the need for concurrent lansoprazole therapy in patients receiving clopidogrel. Monitor response to clopidogrel closely when using clopidogrel with lansoprazole. Whether there are differences among individual proton pump inhibitors is unclear. Other acid-lowering therapies (e.g., H2-receptor antagonists, antacids, etc.) do not appear to share this interaction with clopidogrel.

Enoxacin: Lansoprazole may decrease the absorption of enoxacin.

Indinavir: Omeprazole decreases the absorption of indinavir

Itraconazole: The proton pump inhibitor, lansoprazole, may decrease the absorption of itraconazole.

Ketoconazole: The proton pump inhibitor, lansoprazole, may decrease the absorption of ketoconazole.

Sucralfate: Sucralfate decreases the effect of lansoprazole