Once a PON-1 an enzyme
In March 2010, the FDA added a boxed warning to the blockbuster drug Plavix clopidogrel, an antiplatelet agent, noting that carriers of variants of the liver enzyme cytochrome P450 2C19-present in up to 14% of the population-could experience diminished drug efficacy due to lower levels of drug metabolism. However, thesevariants only account for about a tenth of all cases in which clopidogrel exhibits low efficacy-the rest stem from an as of yet unknown mechanism.1
Now, a European team has put a new enzyme on the map-^paraoxonase-1 (PON-1)-and thinks genotyping the esterase could be a robust marker for identifying patients who are poor Plavix metabolizers.2According to researchers polled by SciBX, the results will have to be confirmed in independent, large-scale studies before the enzyme can be adopted as a clinical marker.
Plavix, a thienopyridine prodrug from Bristol-Myers Squibb Co. and sanofi-aventis Group,is converted in vivoby cytochrome P450 (CYP) enzymes, including cytochrome P450 2C19 (CYP2C19), to its bioactive thiol metabolite. In turn, this metabolite inhibits a key mediator of platelet aggregation called ADP P2RY12 (adenosine diphosphate purinergic receptor P2Y G protein-coupled 12).