title: CYP2C19 Phenoconversion by Routinely Prescribed Proton Pump Inhibitors Omeprazole and Esomeprazole: Clinical Implications for Personalized Medicine.
abstract: The phenotype pantoprazole-(13)C breath test (Ptz-BT) was used to evaluate the extent of phenoconversion of CYP2C19 enzyme activity caused by commonly prescribed proton pump inhibitors (PPI) omeprazole and esomprazole. The Ptz-BT was administered to 26 healthy volunteers and 8 stable cardiovascular patients twice at baseline and after 28 days of PPI therapy to evaluate reproducibility of the Ptz-BT and changes in CYP2C19 enzyme activity (phenoconversion) after PPI therapy. The average intrapatient interday variability in CYP2C19 phenotype (n = 31) determined by Ptz-BT was considerably low (coefficient of variation, 17%). Phenotype conversion resulted in 25 of 26 (96%) nonpoor metabolizer (non-PM) volunteers/patients as measured by the Ptz-BT at baseline and after PPI therapy. The incidence of PM status by phenotype following administration of omeprazole/esomeprazole (known inhibitors of CYP2C19) was 10-fold higher than those who are genetically PMs in the general population, which could have critical clinical implications for personalizing medications primarily metabolized by CYP2C19, such as clopidogrel, PPI, cyclophosphamide, thalidomide, citalopram, clonazepam, diazepam, phenytoin, etc. The Ptz-BT can rapidly (30 minutes) evaluate CYP2C19 phenotype and, more importantly, can identify patients with phenoconversion in CYP2C19 enzyme activity caused by nongenetic factors such as concomitant drugs.
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.).
authors.forename: Martin
authors.initials: M
authors.lastname: Klieber
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.).
authors.forename: Herbert
authors.initials: H
authors.lastname: Oberacher
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.).
authors.forename: Silvia
authors.initials: S
authors.lastname: Hofstaetter
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.).
authors.forename: Beate
authors.initials: B
authors.lastname: Beer
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.).
authors.forename: Martin
authors.initials: M
authors.lastname: Neururer
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.).
authors.forename: Anton
authors.initials: A
authors.lastname: Amann
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.) anilm@isotope.com hannes.alber@uki.at.
authors.forename: Hannes
authors.initials: H
authors.lastname: Alber
authors.affiliation: Breath Research Institute of University of Innsbruck, Dornbirn, Austria (M.K., M.N., A.A.); Department of Anesthesiology and Critical Care Medicine (M.K., M.N., A.A.), Institute of Legal Medicine and Core Facility Metabolomics (H.O., S.H., B.B.), and University Clinic for Internal Medicine III (Cardiology) (H.A.), Innsbruck Medical University, Innsbruck, Austria; Department of Cardiology, Rehabilitation Centre Münster in Tyrol, Münster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.) anilm@isotope.com hannes.alber@uki.at.
authors.forename: Anil
authors.initials: A
authors.lastname: Modak
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism*; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064098:Esomeprazole / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000627:therapeutic use*; D000077402:Pantoprazole; D057285:Precision Medicine / Q000379:methods; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D064098:Esomeprazole