Liu Qian, Dang Da-Sheng, Chen Yu-Feng, Yan Ming, Shi Guo-Bing, Zhao Qing-Chun
Department of Pharmacy, General Hospital of Shenyang Military Area Command, Shenyang, China.
Genet Test Mol Biomarkers. 2012 Nov;16(11):1293-7. doi: 10.1089/gtmb.2012.0119. Epub 2012 Oct 9.
Currently, concerns of clopidogrel and proton pump inhibitors (especially omeprazole) interaction are raised, because they are both metabolized by CYP2C19. What is more, omeprazole can also inhibit the activity of CYP2C19. The study was to compare the influence of omeprazole on platelet inhibition of clopidogrel in various CYP2C19 mutant alleles. One hundred forty-two consecutive patients undergoing elective coronary stenting received aspirin and clopidogrel, and were randomized to omeprazole or the placebo. Enrolled patients were analyzed for adenosine diphosphate-induced platelet aggregation (ADP-Ag), and CYP2C192 and CYP2C193 were identified by polymerase chain reaction-restriction fragment length polymorphism. Of the patients included, 47 (33.1%) belonged to homozygous extensive metabolizers (homEMs) (CYP2C19*1/*1), 70 (49.3%) belonged to heterozygous extensive metabolizers (hetEMs) (*1/*2 or *1/*3), and 25 (17.6%) belonged to poor metabolizers (PMs) (*2/*3 or *2/*2). ADP-Ag had a significant difference among the three genotypic groups (p<0.01). Moreover, the present study revealed that the degree of the interaction between clopidogrel and omeprazole was not homogeneous within the various genotypes of CYP2C19. The difference of ADP-Ag between the patients with and without omeprazole was significantly largest in homEMs (45.7%±14.2% vs. 35.5%±16.0%, p<0.05). However, any significant difference of ADP-Ag between the patients with and without omeprazole was not observed in other two genotypic groups (hetEMs and PMs, p>0.05). In conclusion, concomitant therapy with omeprazole appears to reduce the antiplatelet effect of clopidogrel most significantly in homEMs of CYP2C19.
目前，氯吡格雷与质子泵抑制剂（尤其是奥美拉唑）之间相互作用的问题引发了关注，因为它们均由细胞色素P450 2C19（CYP2C19）代谢。此外，奥美拉唑还可抑制CYP2C19的活性。本研究旨在比较奥美拉唑对不同CYP2C19突变等位基因患者氯吡格雷血小板抑制作用的影响。142例接受择期冠状动脉支架置入术的连续患者服用阿司匹林和氯吡格雷，并随机分为奥美拉唑组或安慰剂组。对入选患者进行二磷酸腺苷诱导的血小板聚集（ADP-Ag）分析，并通过聚合酶链反应-限制性片段长度多态性鉴定CYP2C192和CYP2C193。纳入的患者中，47例（33.1%）为纯合子广泛代谢者（homEMs）（CYP2C19*1/*1），70例（49.3%）为杂合子广泛代谢者（hetEMs）（*1/2或1/*3），25例（17.6%）为慢代谢者（PMs）（*2/3或2/*2）。三个基因型组之间的ADP-Ag有显著差异（p<0.01）。此外，本研究表明，氯吡格雷与奥美拉唑之间相互作用的程度在CYP2C19的不同基因型中并不相同。服用和未服用奥美拉唑患者之间的ADP-Ag差异在homEMs中最为显著（45.7%±14.2%对35.5%±16.0%，p<0.05）。然而，在其他两个基因型组（hetEMs和PMs）中，服用和未服用奥美拉唑患者之间的ADP-Ag未观察到任何显著差异（p>0.05）。总之，奥美拉唑联合治疗似乎在CYP2C19的homEMs中最显著地降低了氯吡格雷的抗血小板作用。
