PT  - JOURNAL ARTICLE
AU  - Klieber, Martin
AU  - Oberacher, Herbert
AU  - Hofstaetter, Silvia
AU  - Beer, Beate
AU  - Neururer, Martin
AU  - Amann, Anton
AU  - Alber, Hannes
AU  - Modak, Anil
TI  - CYP2C19 Phenoconversion by Routinely Prescribed Proton Pump Inhibitors Omeprazole and Esomeprazole: Clinical Implications for Personalized Medicine
AID  - 10.1124/jpet.115.225680
DP  - 2015 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 426--430
VI  - 354
IP  - 3
4099  - http://jpet.aspetjournals.org/content/354/3/426.short
4100  - http://jpet.aspetjournals.org/content/354/3/426.full
SO  - J Pharmacol Exp Ther2015 Sep 01; 354
AB  - The phenotype pantoprazole-13C 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.