Pharmacogenomics of proton pump inhibitors

Proton pump inhibitors (PPIs), such as omeprazole, lansoprazole, rabeprazole, esomeprazole, and pantoprazole, are metabolized by cytochrome P450 isoenzyme 2C19 (CYP2C19) in the liver. There are genetic differences that affect the activity of this enzyme. The genotypes of CYP2C19 are classified into three groups: homozygous extensive metabolizer (homEM), heterozygous extensive metabolizer (hetEM), and poor metabolizer (PM). The pharmacokinetics and pharmacodynamics of PPIs differ among the different CYP2C19 genotype groups. Plasma PPI and intragastric pH levels during PPI treatment are the lowest in the homEM group and the highest in the PM group. These CYP2C19 genotype-dependent differences in pharmacokinetics and pharmacodynamics of PPIs are reflected in the cure rates for gastroesophageal reflux disease and Helicobacter pylori infection with PPI-based therapies. The CYP2C19 genotyping test is a useful tool for deciding on the optimal treatment regimen using a PPI, including a dual (PPI plus antibiotic) or a triple (PPI plus two antibiotics) therapy.