Paraoxonase-1 and clopidogrel efficacy

Clopidogrel active thiol metabolite is formed through 1) a cytochrome P450 (CYP dependent oxidation to a thiolactone : 2-oxoclopidogrel. Then a second CYP dependent oxidation to a sulfenic acid which is reduced by excess glutathione to the active cis -thiol-acid. The 2-oxoclopidogrel is hydrolyzed by paraoxonase PON 1 into an inactive isomer the endo thiol-acid. Thus PON-1 is not involved in the pharmalogical activation of clopidogrel.