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.