Anabel García-Heredia1, Anna Hérnandez-Aguilera1, Isabel Fort-Gallifa1, Jorge Joven1, Vicente Martín-Paredero2 and Jordi Camps1*

  • 1Unitat de Recerca Biomèdica (AGH, AHA, IFG, JJ, JC), Hospital Universitari de Sant Joan
  • 2Service of Angiology, Vascular Surgery and Endosurgery, Hospital Universitari Joan XXIII (VMP), Institut d’Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Spain


Background: Clopidogrel is an antiplatelet agent used in the treatment of vascular diseases. It requires in vivo bio activation linked to the cytochrome P450. Several studies reported that paraoxonase-1 (PON1) was a crucial enzyme in clopidogrel activation, and that patients carrying a variant of the PON1192 gene polymorphism have a high risk of thrombosis. However, these reports were not confirmed by subsequent results. The present study was aimed at investigating whether PON1 deficiency affects the biological action of clopidogrel in mice.

Methods: PON1-deficient mice (n = 50) and wild type animals (n = 50) received different treatments for 3 days: a) clopidogrel, b) aspirin, c) cilostazol, d) clopidogrel + aspirin, and e) clopidogrel + aspirin + cilostazol. Blood was collected for the Platelet Function Analysis (PFA-100).

Results: The different anticoagulant treatments resulted in higher aggregation times in all the mice, compared to the internal PFA control; demonstrating the anti-platelet effect of these compounds. We did not observe any significant alterations on the PFA assay in PON1-deficient mice, relative to wild type animals.

Conclusion: PON1 deficiency does not influence the antiplatelet action of clopidogrel in mice, and supports the proposition that this enzyme is not involved in clopidogrel bio activation.

Keywords: Antiplatelet agents; Clopidogrel; Paraoxonase-1; Vascular diseases

Cardiol Pharmacol 2015