Department of Cardiology, Gaia Hospital Centre, Gaia, Portugal.
Eur J Gastroenterol Hepatol. 2011 May;23(5):396-404. doi: 10.1097/MEG.0b013e3283460110.
Proton pump inhibitors (PPIs) are usually prescribed to patients undergoing dual antiplatelet therapy to decrease the risk of gastrointestinal bleeding. Recent studies have raised concerns that PPIs could reduce clopidogrel's efficacy by competitive inhibition of cytochrome P450 2C19 isoenzyme. All PPIs are metabolized by cytochrome P450 2C19, although to varying degrees, and according to in-vitro studies, pantoprazole is the weakest inhibitor of this isoenzyme. We hypothesized that this drug interaction might not be a class effect.
One month after an acute myocardial infarction 34 consecutive patients undergoing dual antiplatelet therapy were prospectively analyzed. Platelet function was measured (VerifyNow system), in each patient, in three consecutive clinical scenarios: (i) first, after a 1-month washout period, without any PPI, (ii) after a 4-week period taking omeprazole 40 mg, and (iii) after another 1-month washout period, followed by 4-weeks taking pantoprazole 40 mg. In this crossover trial, patients were first randomized to receive either omeprazole or pantoprazole.
We observed a significant reduction in clopidogrel's effect when patients were initiated with omeprazole; the mean P2Y12 reaction units (PRU) increased from 202±52 to 235±58 with omeprazole (P<0.001). With pantoprazole, clopidogrel efficacy was preserved (PRU 215±54, P=0.16). Without any PPI, 26% of patients were 'nonresponders' to clopidogrel (PRU >240) but when patients started omeprazole, this proportion increased to 45 versus 23% with pantoprazole.
In this randomized crossover study analyzing patients after acute myocardial infarction, omeprazole coadministration showed a significant pharmacodynamic interaction with clopidogrel, whereas pantoprazole did not. These data suggest that the clopidogrel-PPIs drug interaction may not be a class effect.
质子泵抑制剂（PPIs）通常被开给正在接受双联抗血小板治疗的患者，以降低胃肠道出血的风险。最近的研究引起了人们的担忧，即 PPIs 通过竞争性抑制细胞色素 P450 2C19 同工酶，可能会降低氯吡格雷的疗效。所有的 PPIs 都通过细胞色素 P450 2C19 代谢，尽管程度不同，但根据体外研究，泮托拉唑是该同工酶最弱的抑制剂。我们假设这种药物相互作用可能不是一种类效应。
34 例连续急性心肌梗死后的患者在接受双联抗血小板治疗后 1 个月进行前瞻性分析。在每个患者的三个连续临床情况下测量血小板功能（VerifyNow 系统）：（i）首先，在 1 个月的洗脱期后，没有任何 PPI；（ii）在服用奥美拉唑 40mg 4 周后；（iii）在又一个 1 个月的洗脱期后，服用泮托拉唑 40mg 4 周。在这个交叉试验中，患者首先随机接受奥美拉唑或泮托拉唑治疗。
当患者开始服用奥美拉唑时，氯吡格雷的效果明显降低；与奥美拉唑相比，血小板聚集单位（PRU）从 202±52 增加到 235±58（P<0.001）。泮托拉唑则保留了氯吡格雷的疗效（PRU 215±54，P=0.16）。没有任何 PPI 时，26%的患者对氯吡格雷反应不佳（PRU >240），但当患者开始服用奥美拉唑时，这一比例增加到 45%，而服用泮托拉唑时则为 23%。
在这项分析急性心肌梗死后患者的随机交叉研究中，奥美拉唑与氯吡格雷联合使用显示出显著的药效学相互作用，而泮托拉唑则没有。这些数据表明，氯吡格雷-PPI 药物相互作用可能不是一种类效应。
