- © 2007 Canadian Medical Association or its licensors
In their study of the risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel, Jung-Won Suh and colleagues observed failures in clopidogrel therapy in patients with the non-expressor genotype for the 3A5 isoenzyme of the cytochrome P450 3A system (*3 allele).1 Because clopidogrel is a prodrug, it is reasonable to hypothesize that its effectiveness will be reduced when metabolism into its active form is reduced. Unfortunately, the lack of any concentration data (of either the parent compound or its metabolite) precludes confirmation of this hypothesis. Without pharmacokinetic data for clopidogrel, the failures in clopidogrel therapy observed by Suh and colleagues cannot be linked to a change in clopidogrel metabolism or in the activity of the cytochrome P450 3A system.
A future examination of these significant observations should include concentration data to confirm a change in clopidogrel pharmacokinetics and establish a pharmacokinetic–pharmacodynamic model. A pharmacogenomically diverse population should also be studied to determine the impact of the cytochrome P450 3A5 non-expressor genotype (*3 allele) on clopidogrel pharmacokinetics and pharmacodynamics. Once a pharmacokinetic–pharmacodynamic model has been established for clopidogrel, clinicians may be able to determine with a single blood draw whether patients require additional antiplatelet therapy.
Footnotes
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The views and opinions expressed are those of the author and not necessarily those of Alberta Blue Cross.
REFERENCE
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