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 (CYP2C192 and3) 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.