Clinical Pharmacy & Pharmacogenomics Life

Figure from "http://www.pharmgkb.org/pathway/PA154424674"

Clopidogrel is a commonly prescribed anti platelet prodrug that is metabolized by several hepatic CYP450 enzymes, predominately CYP2C19.

Clopidogrel 是一常見的抗血小板藥物，而其在被 Cytochrome P-450 代謝前是個沒有活性的前驅藥，而在眾多肝臟 CYP-450 酵素中，CYP2C19 對 clopidogrel 的代謝扮演了重要的角色。

CYP2C19 loss-of-function alleles have been associated with lower active metabolite exposure and decreased platelet responsiveness ex vivo among clopidogrel-treated patients, and increased cardiovascular event (CVE) rates among clopidogrel-treated patients with acute coronary syndromes (ACS) and/or those undergoing percutaneous coronary intervention (PCI).

當病人帶有失去功能（或是功能較差）的 CYP2C19 對偶基因時，病人體內的 clopidogrel 活性代謝物濃度較低，並使得其抗血小板凝集的效果下降，從而致使有急性冠狀動脈症候群 (ACS) 或經皮冠狀動脈介入性治療 (PCI) 的病人發生心血管事件 (CVE) 的風險提高。

Figure from "http://www.hkma.org/chinese/cme/onlinecme/cme201207set.htm"

In addition, a genome-wide association study found CYP2C19*2 to be strongly associated with clopidogrel response & recent large meta-analyses indicate that both heterozygous "intermediate metabolizers (IM)" (e.g., *1/*2) and homozygous "poor metabolizers (PM)" (e.g., *2/*2) clopidogrel-treated ACS/PSI patients are at an increased risk for serious adverse CVEs with a gene-dose effect.

此外，基因體研究發現 CYP2C19*2 這個基因多型性與 clopidogrel 的治療反應具有強烈的相關性，而大型的綜合分析也指出，當 ACS/PCI 病患服用 clopidogrel 時，本身為 CYP2C19*2 中度代謝者（基因型為 CYP2C19*2 異型合子）與低度代謝者（基因型為 CYP2C19*2 同型合子）可能存在著「基因－劑量效應」，致使其嚴重的心血管事件發生率較高。

Adapted from J Am Coll Cardiol. 2010;56(2):134-143.






Wind Chang M.S.

Nov 4, 2012