Individual variability in the disposition of and response to clopidogrel: pharmacogenomics and beyond.
The widespread use of clopidogrel alone or in combination with aspirin has significantly benefited patients with acute coronary syndrome who are managed medically or by percutaneous coronary intervention and stent implantation, greatly improving their survival. Emerging data have documented that the clopidogrel response may vary from person to person and even from disease to disease, and that genetic and nongenetic factors contribute to that variability. Genetic polymorphisms affecting clopidogrel metabolic bioactivation and platelet function may be responsible, each exerting a small effect. CYP2C19 *2, *3 and *17, CYP2C9 *2 and *3, MDR1*2, and functional variants in the genes encoding platelet membrane receptors and intracellular signaling proteins are involved, and other genetic factors remain to be identified. In addition, nongenetic factors may be influential covariates, such as ethnicity, gender, age, body weight, co-existing diseases, drug-drug interactions, and other factors to be determined. Each piece of the puzzle would be useful to bridge and delineate identified knowledge gaps and to determine future research needs for the risk prediction of fatal complications associated with inadequate clopidogrel therapy in patient care.
Hospital Central Laboratory, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China. hongg.xie@gmail.com
Hong-Guang
HG
Xie
Jian-Jun
JJ
Zou
Zuo-Ying
ZY
Hu
Jun-Jie
JJ
Zhang
Fei
F
Ye
Shao-Liang
SL
Chen
D054058:Acute Coronary Syndrome / Q000628:therapy; D000077144:Clopidogrel; D004341:Drug Evaluation / Q000379:methods; D006801:Humans; D007206:Individuality; D010597:Pharmacogenetics / Q000379:methods*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D018570:Risk Assessment; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine