PMID- 26815196
OWN - NLM
STAT- MEDLINE
DCOM- 20160831
LR  - 20181202
IS  - 1752-7163 (Electronic)
IS  - 1752-7155 (Linking)
VI  - 10
IP  - 1
DP  - 2016 Jan 27
TI  - Changes in CYP2C19 enzyme activity evaluated by the [(13)C]-pantoprazole breath 
      test after co-administration of clopidogrel and proton pump inhibitors following 
      percutaneous coronary intervention and correlation to platelet reactivity.
PG  - 017104
LID - 10.1088/1752-7155/10/1/017104 [doi]
AB  - Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is used for the 
      prevention of cardiovascular events following percutaneous coronary intervention 
      (PCI). These agents increase the risk of gastrointestinal bleeding. To prevent 
      these events, proton pump inhibitors (PPI) are routinely prescribed. It has been 
      reported that with the exception of pantoprazole and dexlanzoprazole, PPIs can 
      impede conversion of clopidogrel by cytochrome P450 2C19 (CYP2C19) to its active 
      metabolite, a critical step required for clopidogrel efficacy. Changes in CYP2C19 
      enzyme activity (phenotype) and its correlation with platelet reactivity 
      following PPI therapy has not yet been fully described. In this study we 
      attempted to determine if the [ (13)C]-pantoprazole breath test (Ptz-BT) can 
      evaluate changes in CYP2C19 enzyme activity (phenoconversion) following the 
      administration of PPI in coronary artery disease (CAD) patients treated with DAPT 
      after PCI. Thirty (30) days after successful PCI with stent placement, 59 
      patients enrolled in the Evaluation of the Influence of Statins and Proton Pump 
      Inhibitors on Clopidogrel Antiplatelet Effects (SPICE) trial (ClinicalTrials.gov 
      Identifier: NCT00930670) were recruited to participate in this sub study. 
      Patients were randomized to one of 4 antacid therapies (omeprazole, esomeprazole. 
      pantoprazole or ranitidine). Subjects were administered the Ptz-BT and platelet 
      function was evaluated by vasodilator-stimulated phosphoprotein (VASP) 
      phosphorylation and light transmittance aggregometry before and 30 d after 
      treatment with antacid therapy. Patients randomized to esomeprazole and 
      omeprazole had greater high on-treatment platelet reactivity and lowering of 
      CYP2C19 enzyme activity at Day 60 after 30 d of PPI therapy. Patients randomized 
      to ranitidine and pantoprazole did not show any changes in platelet activity or 
      CYP 2C19 enzyme activity. In patients treated with esomeprazole and omeprazole, 
      changes in CYP2C19 enzyme activity (phenoconversion) correlated well with changes 
      in platelet reactivity. Co-administration of omeprazole or esomeprazole in 
      patients treated with clopidogrel results in lower CYP2C19 enzyme activity and 
      increased platelet reactivity as measured by VASP phosphorylation test while 
      patients given pantoprazole or ranitidine did not show any significant changes in 
      CYP2C19 enzyme activity and platelet reactivity.
FAU - Harvey, Adrien
AU  - Harvey A
AD  - Centre de recherche de l'Institut universitaire de cardiologie et pneumologie de 
      Quebec, Quebec, QC, Canada.
FAU - Modak, Anil
AU  - Modak A
FAU - Dery, Ugo
AU  - Dery U
FAU - Roy, Melanie
AU  - Roy M
FAU - Rinfret, Stephane
AU  - Rinfret S
FAU - Bertrand, Olivier F
AU  - Bertrand OF
FAU - Larose, Eric
AU  - Larose E
FAU - Rodes-Cabau, Josep
AU  - Rodes-Cabau J
FAU - Barbeau, Gerald
AU  - Barbeau G
FAU - Gleeton, Onil
AU  - Gleeton O
FAU - Nguyen, Can Manh
AU  - Nguyen CM
FAU - Proulx, Guy
AU  - Proulx G
FAU - Noel, Bernard
AU  - Noel B
FAU - Roy, Louis
AU  - Roy L
FAU - Paradis, Jean-Michel
AU  - Paradis JM
FAU - De Larochelliere, Robert
AU  - De Larochelliere R
FAU - Dery, Jean-Pierre
AU  - Dery JP
LA  - eng
SI  - ClinicalTrials.gov/NCT00930670
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20160127
PL  - England
TA  - J Breath Res
JT  - Journal of breath research
JID - 101463871
RN  - 0 (2-Pyridinylmethylsulfinylbenzimidazoles)
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - 0 (Proton Pump Inhibitors)
RN  - 884KT10YB7 (Ranitidine)
RN  - A74586SNO7 (Clopidogrel)
RN  - D8TST4O562 (Pantoprazole)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2C19)
RN  - KG60484QX9 (Omeprazole)
RN  - N3PA6559FT (Esomeprazole)
RN  - OM90ZUW7M1 (Ticlopidine)
SB  - IM
MH  - 2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use
MH  - Blood Platelets/*drug effects/metabolism
MH  - *Breath Tests
MH  - Clopidogrel
MH  - Cytochrome P-450 CYP2C19/*metabolism
MH  - Drug Interactions
MH  - Esomeprazole/administration & dosage/therapeutic use
MH  - Humans
MH  - Omeprazole/administration & dosage/therapeutic use
MH  - Pantoprazole
MH  - Percutaneous Coronary Intervention
MH  - Platelet Aggregation Inhibitors/*administration & dosage/therapeutic use
MH  - Platelet Function Tests
MH  - Proton Pump Inhibitors/administration & dosage/*therapeutic use
MH  - Ranitidine/administration & dosage/therapeutic use
MH  - Ticlopidine/administration & dosage/*analogs & derivatives/therapeutic use
EDAT- 2016/01/28 06:00
MHDA- 2016/09/01 06:00
CRDT- 2016/01/28 06:00
PHST- 2016/01/28 06:00 [entrez]
PHST- 2016/01/28 06:00 [pubmed]
PHST- 2016/09/01 06:00 [medline]
AID - 10.1088/1752-7155/10/1/017104 [doi]
PST - epublish
SO  - J Breath Res. 2016 Jan 27;10(1):017104. doi: 10.1088/1752-7155/10/1/017104.