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Review
. 2020 Dec;8(6):e00686.
doi: 10.1002/prp2.686.

Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy

Bhawani Yasassri Alvitigala  1 , Lallindra Viranjan Gooneratne  2 , Godwin Roger Constantine  3 , Rajapaksha Arachchige Namal Kumarasiri Wijesinghe  4 , Liyanage Dona Ashanthi Menuka Arawwawala  5
Affiliations
Review

Pharmacokinetic, pharmacodynamic, and pharmacogenetic assays to monitor clopidogrel therapy

Bhawani Yasassri Alvitigala et al. Pharmacol Res Perspect. 2020 Dec.

Abstract

Clopidogrel is the most common and widely used antiplatelet agent for patients with coronary artery disease following confirmation by electrocardiographic studies. The nonresponsiveness of patients to clopidogrel and the possibility of testing for clopidogrel resistance by platelet function assays (PFA) are contentious issues. Light transmission aggregometry (LTA) is considered as the gold standard test among all PFA. In this review, the most commonly used PFA used for monitoring the effect of clopidogrel, LTA, vasodilator-stimulated phosphoprotein assay phosphorylation, rotational thromboelastometry (ROTEM) delta and ROTEM platelet, thromboelastography, PFA-100, VerifyNow P2Y12 assay, Multiplate analyzer, Plateletworks assay and pharmacogenetic studies, are comparatively discussed including their principles of action, advantages, and disadvantages. VerifyNow P2Y12 assay can be accepted as the ideal point of care test out of the discussed assays. However, modified assays are required which could overcome the limitations associated with currently available assays.

Keywords: HPLC; clopidogrel; pharmacogenetic assays; platelet function assays.

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Conflict of interest statement

None declared.

Figures

FIGURE 1
FIGURE 1
Metabolic activation of clopidogrel prodrug in patients. CLPM, clopidogrel metabolite; CTM, converted to thiol metabolite of clopidogrel
FIGURE 2
FIGURE 2
PFA available to monitor the effect of clopidogrel in patients with CAD. HPLC‐MS, high performance liquid chromatography‐mass spectrometry; LTA, light transmission aggregometry; PFA, platelet function assay; ROTEM, rotational thromboelastometry; TEG, thromboelastography; VASP, vasodilator‐stimulated phosphoprotein
FIGURE 3
FIGURE 3
Differentiation of results obtained from conventional and modifies light transmission aggregometry performed on clopidogrel responder and non‐responder patients (Bagoly et al, 2013). 44 Conventional adenosine diphosphate (ADP) aggregation (without prostaglandin E1 [PGE1]) is shown in the left side and P2Y12 specific ADP aggregation with PGE1 is shown in right side. Top graphs shows the samples obtained from clopidogrel responder patients and below shows the samples obtained from clopidogrel resistant patient
FIGURE 4
FIGURE 4
ADP‐induced platelet aggregation curve obtained from light transmission aggregometry before and after clopidogrel therapy (as cited by Lordkipanidze et al, 2009). 99 ADP, adenosine diphosphate
See this image and copyright information in PMC

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