Original and generic clopidogrel: A comparison of antiplatelet effects and active metabolite concentrations in patients without polymorphisms in the ABCB1 gene and the allele variants CYPC19*2 and *3

Abstract

Ticagrelor and prasugrel are widely used as antiplatelet therapy after coronary angioplasty. However, there is a group of patients with indications for clopidogrel treatment. This population includes patients with chronic or acute coronary syndrome who are treated invasively and have contraindications to the use of novel antiplatelet drugs due to antithrombotic treatment (particularly with non-vitamin K antagonist oral anticoagulants). A wide range of generic forms of clopidogrel are available on the market. However, it is unclear whether they are as effective as the originator drug. In the current study, we aimed to assess the concentrations of the active metabolite of clopidogrel and its effect on platelet aggregation inhibition in patients receiving the originator drug in comparison with those receiving generic clopidogrel. We enrolled 22 healthy individuals without polymorphisms in the ABCB1 gene and the allele variants CYPC19*2 and CYPC19*3. All participants received a loading dose of clopidogrel (600 mg), followed by a maintenance dose of 75 mg for the next 3 days. On day 3, blood samples were obtained 1 h after drug administration to assess active metabolite concentrations using liquid chromatography with tandem mass spectrometry. In each participant, platelet aggregation was assessed with light transmission aggregometry after 5-μmol/L and 10-μmol/L adenosine diphosphate (ADP) stimulation. Assays were performed for the originator clopidogrel and 2 different generic groups. The mean ± standard deviation (SD) concentrations of active clopidogrel did not differ between the originator drug and 2 generic products with clopidogrel (12.7±5 pg/μL compared to 13.0 ±4 pg/μL compared to 14.4 ±4 pg/μL). Platelet aggregation inhibition after stimulation with 5 μmol/L and 10 μmol/L ADP was similar for all preparations. In comparison with original clopidogrel, the use of its generic form does not affect the blood concentrations of the active metabolite or its antiplatelet effect.