PMID- 27991432
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20181202
IS  - 1752-7163 (Electronic)
IS  - 1752-7155 (Linking)
VI  - 10
IP  - 4
DP  - 2016 Dec 17
TI  - The effect of proton pump inhibitors on the CYP2C19 enzyme activity evaluated by 
      the pantoprazole-(13)C breath test in GERD patients: clinical relevance for 
      personalized medicine.
PG  - 046017
AB  - 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-(13)C 
      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.
FAU - Modak, Anil S
AU  - Modak AS
AD  - Cambridge Isotope Laboratories, Inc., Tewksbury, MA 01876, USA. Author to whom 
      any correspondence should be addressed.
FAU - Klyarytska, Iryna
AU  - Klyarytska I
FAU - Kriviy, Valerij
AU  - Kriviy V
FAU - Tsapyak, Tatjana
AU  - Tsapyak T
FAU - Rabotyagova, Yliya
AU  - Rabotyagova Y
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20161217
PL  - England
TA  - J Breath Res
JT  - Journal of breath research
JID - 101463871
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Biomarkers)
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (Proton Pump Inhibitors)
RN  - D8TST4O562 (Pantoprazole)
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  - Aged
MH  - Biomarkers/metabolism
MH  - Breath Tests/*methods
MH  - Carbon Radioisotopes
MH  - Cytochrome P-450 CYP2C19/*metabolism
MH  - Esomeprazole/therapeutic use
MH  - Female
MH  - Gastroesophageal Reflux/*diagnosis/*drug therapy
MH  - Genetic Association Studies
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Omeprazole/therapeutic use
MH  - Pantoprazole
MH  - Pharmacogenetics
MH  - *Precision Medicine
MH  - Proton Pump Inhibitors/*therapeutic use
MH  - Young Adult
EDAT- 2016/12/20 06:00
MHDA- 2017/09/19 06:00
CRDT- 2016/12/20 06:00
PHST- 2016/12/20 06:00 [entrez]
PHST- 2016/12/20 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
AID - 10.1088/1752-7163/10/4/046017 [doi]
PST - epublish
SO  - J Breath Res. 2016 Dec 17;10(4):046017. doi: 10.1088/1752-7163/10/4/046017.