Lansoprazole response

Proton pump inhibitors (PPIs) inhibit the final pathway of acid production, which leads to inhibition of gastric acid secretion. PPIs are widely used in the treatment and prevention of many conditions including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, H. pylori infection, and pathological hypersecretory conditions. The first-generation inhibitors omeprazole, lansoprazole and pantoprazole are extensively metabolized by the cytochrome P450 isoform CYP2C19 and to a lesser extent by CYP3A4. The second-generation PPI dexlansoprazole appears to share a similar metabolic pathway to lansoprazole. CYP2C19 genotypes have been linked to PPI exposure and in turn to PPI efficacy and adverse effects. CYP2C19 intermediate (IMs) and poor metabolizers (PMs) have been associated with decreased clearance and increased plasma concentrations of the first-generation PPIs, which leads to increased treatment success compared to CYP2C19 normal metabolizers (NMs). However, higher exposure and long-term use of PPIs have also been associated with adverse effects. CYP2C19 ultrarapid (UMs) and rapid metabolizers (RMs) have shown increased metabolism compared to NMs, which may increase the risk of treatment failure. Guidelines regarding the use of pharmacogenomic tests in dosing for PPIs have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the CPIC and PharmGKB websites. The CPIC guideline provides specific therapeutic recommendations for four PPIs (omeprazole, lansoprazole, pantoprazole, and dexlansoprazole) based on CYP2C19 genotype. [from PharmGKB]