Prediction of clopidogrel low responders by a rapid CYP2C19 activity test

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 ( 13co 2/ 12co 2) in expiration gas between before and after 13c-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 (em s) and intermediate metabolizers (im s) (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,p2y 12 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 13c-pantoprazole breath test can detect cyp2c19 pms and predict low responders to clopidogrel rapidly.