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Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists


Coronary artery disease remains the major cause of mortality worldwide. Antiplatelet drugs such as acetylsalicylic acid and P2Y12 receptor antagonists are cornerstone treatments for the prevention of thrombotic events in patients with coronary artery disease. Clopidogrel has long been the gold standard but has major pharmacological limitations such as a slow onset and long duration of effect, as well as weak platelet inhibition with high inter-individual pharmacokinetic and pharmacodynamic variability. There has been a strong need to develop potent P2Y12 receptor antagonists with more favorable pharmacological properties. Prasugrel and ticagrelor are more potent and have a faster onset of action; however, they have shown an increased bleeding risk compared with clopidogrel. Cangrelor is highly potent and has a very rapid onset and offset of effect; however, its indication is limited to P2Y12 antagonist-naïve patients undergoing percutaneous coronary intervention. Two novel P2Y12 receptor antagonists are currently in clinical development, namely vicagrel and selatogrel. Vicagrel is an analog of clopidogrel with enhanced and more efficient formation of its active metabolite. Selatogrel is characterized by a rapid onset of action following subcutaneous administration and developed for early treatment of a suspected acute myocardial infarction. This review article describes the clinical pharmacology profile of marketed P2Y12 receptor antagonists and those under development focusing on pharmacokinetic, pharmacodynamic, and drug–drug interaction liability.

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The authors thank Dr. Andrea Henrich for her assistance with the figure preparation.

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Correspondence to Uta Schilling.

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The studies involving selatogrel discussed in this review were funded by Idorsia Pharmaceuticals Ltd.

Conflict of interest

Uta Schilling is a full-time employee of Idorsia Pharmaceuticals Ltd. Mike Ufer and Jasper fDingemanse are full-time employees of Idorsia Pharmaceuticals Ltd and owners of stocks/ stock options. Selatogrel is currently in development by Idorsia Pharmaceuticals Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the article.

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Schilling, U., Dingemanse, J. & Ufer, M. Pharmacokinetics and Pharmacodynamics of Approved and Investigational P2Y12 Receptor Antagonists. Clin Pharmacokinet (2020).

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