title: The effect of proton pump inhibitors on the CYP2C19 enzyme activity evaluated by the pantoprazole-13C breath test in GERD patients: clinical relevance for personalized medicine.
abstract: Patients with gastroesophageal reflux disease (GERD) are routinely prescribed one of the six FDA approved proton pump inhibitors (PPI). All of these PPI are inhibitors of CYP2C19 enzyme to varying degrees. The phenotype pantoprazole-13C breath test (Ptz-BT) was used to identify patients who are poor metabolizers (PM) and the extent of phenoconversion of CYP2C19 enzyme activity caused by four PPI (omeprazole, esomprazole pantoprazole and rabeprazole) in 54 newly diagnosed GERD patients prior to initiating randomly selected PPI therapy and 30 d after PPI therapy. The phenoconversion after 30 d of PPI therapy in GERD patients was statistically significant (p  =0.001) with omeprazole/esomeprazole (n  =  27) strong CYP2C19 inhibitors, while there was no change in CYP2C19 enzyme activity (p  =  0.8) with pantoprazole/ rabeprazole (n  =  27), weak CYP2C19 inhibitors. The concommitant use of omeprazole/esomeprazole, therefore, could have critical clinical relevance in individualizing medications metabolized primarily by CYP2C19 such as PPI, clopidogrel, phenytoin, cyclophosphamide, thalidomide, citalopram, clonazepam, diazepam, proguanil, tivantinib etc. The rapid (30 min), in vivo, and non-invasive phenotype Ptz-BT can evaluate CYP2C19 enzyme activity. More importantly, it can identify GERD patients with low CYP2C19 enzyme activity (PM), caused by PPI or other concomitant medications, who would benefit from dose adjustments to maintain efficacy and avoid toxicity. The existing CYP2C19 genotype tests cannot predict the phenotype nor can it detect phenoconversion due to non genetic factors.
authors.affiliation: Cambridge Isotope Laboratories, Inc., Tewksbury, MA 01876, USA. Author to whom any correspondence should be addressed.
authors.forename: Anil S
authors.initials: AS
authors.lastname: Modak
authors.forename: Iryna
authors.initials: I
authors.lastname: Klyarytska
authors.forename: Valerij
authors.initials: V
authors.lastname: Kriviy
authors.forename: Tatjana
authors.initials: T
authors.lastname: Tsapyak
authors.forename: Yliya
authors.initials: Y
authors.lastname: Rabotyagova
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests / Q000379:methods*; D002250:Carbon Radioisotopes; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism*; D064098:Esomeprazole / Q000627:therapeutic use; D005260:Female; D005764:Gastroesophageal Reflux / Q000175:diagnosis* / Q000188:drug therapy*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use; D000077402:Pantoprazole; D010597:Pharmacogenetics; D057285:Precision Medicine; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D015415:Biomarkers; D002250:Carbon Radioisotopes; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D064098:Esomeprazole