Prasugrel Therapy and CYP Genotype

Laura Dean, Victoria M. Pratt, Stuart A. Scott, Munir Pirmohamed, Bernard Esquivel, Brandi L. Kattman, Adriana J. Malheiro, Laura Dean, Victoria M. Pratt, Stuart A. Scott, Munir Pirmohamed, Bernard Esquivel, Brandi L. Kattman, Adriana J. Malheiro

Excerpt

Prasugrel is a third-generation thienopyridine platelet inhibitor used in the management of patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prasugrel is used to reduce thrombotic cardiovascular events, such as stent thrombosis, myocardial infarction, and stroke in these patients. Prasugrel, along with other antiplatelet agents such as clopidogrel and ticagrelor, inhibits platelet activation by irreversibly binding to the platelet receptor, P2RY12.

Prasugrel is metabolized to its active metabolite primarily by CYP3A5 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19. The FDA-approved label for prasugrel states that genetic variations in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 genes do not have a relevant effect on prasugrel pharmacokinetics and the generation of its active metabolite or its inhibition of platelet aggregation in healthy subjects, patients with stable atherosclerosis, or ACS (1).

Another commonly prescribed antiplatelet is the second-generation thienopyridine clopidogrel, which is bioactivated primarily by CYP2C19. Consequently, clopidogrel is less effective among patients with decreased or no function variant alleles in the CYP2C19 gene. In contrast, CYP2C19 variants are not associated with a decrease in effectiveness of prasugrel, which is a more potent antiplatelet agent than clopidogrel, but has a higher risk of bleeding (2-5).

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Source: PubMed

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