Prediction of clopidogrel low responders by a rapid CYP2C19 activity test

J Atheroscler Thromb. 2012;19(2):186-93. doi: 10.5551/jat.10009. Epub 2011 Dec 14.


Aim: Clopidogrel, an essential drug for the prevention of stent thrombosis, is a prodrug activated by CYP enzyme family including CYP2C19. It is known that activity-defective polymorphisms of CYP2C19 (CYP2C19*2 and*3) are associated with reduced clopidogrel efficacy and poor prognosis. Recently, the (13)C-pantoprazole breath test is developed to evaluate the CYP2C19 activity. The aim of this study is to evaluated the efficiency of the CYP2C19 activity test as a predictor of antiplatelet effect of clopidogrel.

Methods: The CYP2C19 activity and the antiplatelet effect of clopidogrel were evaluated in 27 healthy volunteers. Change of the carbon isotope ratios ((13)CO(2)/(12)CO(2)) in expiration gas between before and after (13)C-pantoprazole intake was evaluated as delta over baseline (DOB) ratio (‰).

Results: DOB at 30 min was significantly lower in poor metabolizers (PMs) than extensive metabolizers (EMs) and intermediate metabolizers (IMs) (EM vs. PM, p=0.0108; IM vs. PM, p=0.016). The antiplatelet effect of clopidogrel was significantly different in three groups (inhibition of platelet aggregation: p=0.0148, P2Y12 reaction unit: p=0.0241). DOB at 30 min was correlated with the antiplatelet effect of clopidogrel. A cut-off value of DOB at 30 min below 1.0‰ predicted PMs with 96% specificity and 100% sensitivity.

Conclusions: The (13)C-pantoprazole breath test can detect CYP2C19 PMs and predict low responders to clopidogrel rapidly.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / pharmacokinetics
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism*
  • Breath Tests*
  • Carbon Radioisotopes / pharmacokinetics
  • Clopidogrel
  • Cytochrome P-450 CYP2C19
  • Genotype
  • Humans
  • Male
  • Pantoprazole
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Polymorphism, Genetic / genetics
  • Prognosis
  • Proton Pump Inhibitors / pharmacokinetics
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Tissue Distribution


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Carbon Radioisotopes
  • Platelet Aggregation Inhibitors
  • Proton Pump Inhibitors
  • Clopidogrel
  • Pantoprazole
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • Ticlopidine