PMID- 26159874 OWN - NLM STAT- MEDLINE DCOM- 20151006 LR - 20181202 IS - 1521-0103 (Electronic) IS - 0022-3565 (Linking) VI - 354 IP - 3 DP - 2015 Sep TI - CYP2C19 Phenoconversion by Routinely Prescribed Proton Pump Inhibitors Omeprazole and Esomeprazole: Clinical Implications for Personalized Medicine. PG - 426-30 LID - 10.1124/jpet.115.225680 [doi] AB - 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. CI - Copyright (c) 2015 by The American Society for Pharmacology and Experimental Therapeutics. FAU - Klieber, Martin AU - Klieber M AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.). FAU - Oberacher, Herbert AU - Oberacher H AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.). FAU - Hofstaetter, Silvia AU - Hofstaetter S AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.). FAU - Beer, Beate AU - Beer B AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.). FAU - Neururer, Martin AU - Neururer M AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.). FAU - Amann, Anton AU - Amann A AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.). FAU - Alber, Hannes AU - Alber H AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.) anilm@isotope.com hannes.alber@uki.at. FAU - Modak, Anil AU - Modak A AD - 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 Munster in Tyrol, Munster, Austria (H.A.); and Cambridge Isotopes Laboratories, Tewksbury, Massachusetts (A.M.) anilm@isotope.com hannes.alber@uki.at. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150709 PL - United States TA - J Pharmacol Exp Ther JT - The Journal of pharmacology and experimental therapeutics JID - 0376362 RN - 0 (2-Pyridinylmethylsulfinylbenzimidazoles) RN - 0 (Enzyme Inhibitors) RN - 0 (Proton Pump Inhibitors) RN - D8TST4O562 (Pantoprazole) RN - EC 1.14.14.1 (CYP2C19 protein, human) RN - EC 1.14.14.1 (Cytochrome P-450 CYP2C19) RN - KG60484QX9 (Omeprazole) RN - N3PA6559FT (Esomeprazole) SB - IM MH - 2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use MH - Adolescent MH - Adult MH - Cytochrome P-450 CYP2C19/*metabolism MH - Drug Interactions/physiology MH - Enzyme Inhibitors/pharmacology MH - Esomeprazole/*therapeutic use MH - Female MH - Humans MH - Male MH - Middle Aged MH - Omeprazole/*therapeutic use MH - Pantoprazole MH - Precision Medicine/methods MH - Proton Pump Inhibitors/*therapeutic use MH - Reproducibility of Results MH - Young Adult EDAT- 2015/07/15 06:00 MHDA- 2015/10/07 06:00 CRDT- 2015/07/11 06:00 PHST- 2015/05/05 00:00 [received] PHST- 2015/07/08 00:00 [accepted] PHST- 2015/07/11 06:00 [entrez] PHST- 2015/07/15 06:00 [pubmed] PHST- 2015/10/07 06:00 [medline] AID - jpet.115.225680 [pii] AID - 10.1124/jpet.115.225680 [doi] PST - ppublish SO - J Pharmacol Exp Ther. 2015 Sep;354(3):426-30. doi: 10.1124/jpet.115.225680. Epub 2015 Jul 9.