The effect of proton pump inhibitors on the CYP2C19enzyme activity evaluated by the pantoprazole-13Cbreath test in GERD patients: clinical relevance forpersonalized medicine

Patients with gastroesophageal reflux disease (GERD) areroutinely prescribed one of the six FDA approved proton pumpinhibitors (PPI). All of these PPI are inhibitors of CYP2C19enzyme to varying degrees. The phenotypepantoprazole-13C breath test (Ptz-BT) was used toidentify patients who are poor meta...

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Bibliographic Details
Published in:Journal of breath research 2016-12, Vol.10 (4), p.046017
Main Authors: Modak, Anil S, Klyarytska, Iryna, Kriviy, Valerij, Tsapyak, Tatjana, Rabotyagova, Yliya
Format: Article
Language:English
Subjects:
Enzymes
Gastroesophageal reflux
Online Access:Get full text
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Summary:Patients with gastroesophageal reflux disease (GERD) areroutinely prescribed one of the six FDA approved proton pumpinhibitors (PPI). All of these PPI are inhibitors of CYP2C19enzyme to varying degrees. The phenotypepantoprazole-13C breath test (Ptz-BT) was used toidentify patients who are poor metabolizers (PM) and the extentof phenoconversion of CYP2C19 enzyme activity caused by four PPI(omeprazole, esomprazole pantoprazole and rabeprazole) in 54newly diagnosed GERD patients prior to initiating randomlyselected PPI therapy and 30 d after PPI therapy.The phenoconversion after 30 d of PPI therapy in GERD patientswas statistically significant (p  =0.001) withomeprazole/esomeprazole (n  =  27) strongCYP2C19 inhibitors, while there was no change in CYP2C19 enzymeactivity (p  =  0.8) with pantoprazole/rabeprazole (n  =  27), weak CYP2C19inhibitors. The concommitant use of omeprazole/esomeprazole,therefore, could have critical clinical relevance inindividualizing medications metabolized primarily by CYP2C19such 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 enzymeactivity. More importantly, it can identify GERD patients withlow CYP2C19 enzyme activity (PM), caused by PPI or otherconcomitant medications, who would benefit from dose adjustmentsto maintain efficacy and avoid toxicity. The existing CYP2C19genotype tests cannot predict the phenotype nor can it detectphenoconversion due to non genetic factors.
ISSN:1752-7155
1752-7163
DOI:10.1088/1752-7163/10/4/046017