Pharmacol Ther. 2010 Oct 18. [Epub ahead of print]
Individual variability in the disposition of and response to clopidogrel: Pharmacogenomics and beyond.
Xie HG, Chen SL, Hu ZY, Zhang JJ, Ye F, Zou JJ.
Hospital Central Laboratory, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China; Department of Clinical Pharmacology, Nanjing First Hospital Affiliated to Nanjing Medical University, and Nanjing Cardiovascular Hospital, Nanjing, Jiangsu, China.
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 contributory, each exerting a small effect. Contributions from 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 involved, 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 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.
Copyright © 2010. Published by Elsevier Inc.
PMID: 20965214 [PubMed - as supplied by publisher]Individual variability in the disposition of and r... [Pharmacol Ther. 2010] - PubMed result
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