Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
J Atheroscler Thromb. 2012;19(2):186-93. doi: 10.5551/jat.10009. Epub 2011 Dec 14.
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.
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 (‰).
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.
The (13)C-pantoprazole breath test can detect CYP2C19 PMs and predict low responders to clopidogrel rapidly.
氯吡格雷是预防支架内血栓形成的基本药物，是一种由包括 CYP2C19 在内的 CYP 酶家族激活的前体药物。已知 CYP2C19 活性缺陷多态性（CYP2C192 和3）与氯吡格雷疗效降低和预后不良有关。最近，（13）C-泮托拉唑呼吸试验被开发用于评估 CYP2C19 活性。本研究旨在评估 CYP2C19 活性试验作为氯吡格雷抗血小板作用预测因子的效率。
在 27 名健康志愿者中评估 CYP2C19 活性和氯吡格雷的抗血小板作用。呼气中碳同位素比率（（13）CO2/（12）CO2）的变化在（13）C-泮托拉唑摄入前后作为基线的差值（DOB）比（‰）进行评估。
30 分钟时，弱代谢者（PMs）的 DOB 明显低于广泛代谢者（EMs）和中间代谢者（IMs）（EM 与 PM，p=0.0108；IM 与 PM，p=0.016）。三组之间氯吡格雷的抗血小板作用存在显著差异（血小板聚集抑制：p=0.0148，P2Y12 反应单位：p=0.0241）。30 分钟时的 DOB 与氯吡格雷的抗血小板作用相关。30 分钟时 DOB 低于 1.0‰的截止值可预测 PMs，特异性为 96%，敏感性为 100%。
（13）C-泮托拉唑呼吸试验可检测 CYP2C19 PMs，并快速预测氯吡格雷低反应者。
