title: Laboratory evaluation of clopidogrel responsiveness by platelet function and genetic methods.
abstract: Clopidogrel is a widely used antiplatelet agent that irreversibly inhibits platelet P2Y12 ADP receptors after conversion to an active metabolite. There are a number of laboratory tests capable of detecting clopidogrel-induced platelet inhibition and published literature correlates suboptimal clopidogrel response to adverse cardiovascular outcomes. Genetic polymorphisms are thought to affect conversion of the prodrug to the active metabolite, and the FDA has recently added a black-box warning to clopidogrel to highlight the effects of these polymorphisms on drug bioavailability and to inform prescribers about the availability of genetic testing. For these reasons, there is growing interest in the use of laboratory tests to monitor patients treated with clopidogrel. This article summarizes the currently available laboratory testing, including platelet function tests and genotyping for CYP2C19 variants.
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center and ARUP Laboratories Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA. kristi.smock@aruplab.com
authors.forename: Kristi J
authors.initials: KJ
authors.lastname: Smock
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Saunders
authors.forename: George M
authors.initials: GM
authors.lastname: Rodgers
authors.forename: Vandita
authors.initials: V
authors.lastname: Johari
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001682:Biological Availability; D001711:Biotransformation; D001792:Blood Platelets / Q000187:drug effects*; D000077144:Clopidogrel; D065731:Cytochrome P-450 CYP2C19; D016903:Drug Monitoring / Q000379:methods*; D060005:Genotyping Techniques; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011355:Prodrugs / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D058921:Purinergic P2Y Receptor Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D058925:Receptors, Purinergic P2Y12 / Q000737:chemistry; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D011355:Prodrugs; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine