Pharmacogenomic testing: the case for CYP2C19 proton pump inhibitor gene-drug pairs

Pharmacogenomics. 2014 Aug;15(11):1405-16. doi: 10.2217/pgs.14.103.

Abstract

The use of proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux and related diseases is increasing, especially in the pediatric population. Prolonged use of PPIs has been associated with several adverse effects, including potentially life-threatening gastric and respiratory infections, which are related to dose or to the degree of gastric acid suppression. Genetic variation in the CYP2C19 gene gives rise to poor and extensive metabolizer phenotypes, which influence PPI clearance, efficacy and exposure. A recent paper linked lansoprazole-associated respiratory infections in children with the poor metabolizer phenotype. The case is made for implementing pharmacogenomic testing for the CYP2C19-PPI gene-drug pair and to dose accordingly in order to minimize PPI-associated infections.

Keywords: CYP2C19; adverse events; gene; infection; pharmacogenomic; proton pump inhibitors; testing.

MeSH terms

  • Cytochrome P-450 CYP2C19 / genetics*
  • Cytochrome P-450 CYP2C19 / metabolism*
  • Drug Interactions / genetics*
  • Gastroesophageal Reflux / genetics
  • Genetic Variation / genetics*
  • Humans
  • Lansoprazole / adverse effects
  • Pharmacogenetics / methods
  • Proton Pump Inhibitors / adverse effects*
  • Respiratory Tract Infections / genetics

Substances

  • Proton Pump Inhibitors
  • Lansoprazole
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19