Pharmacology of the new P2Y12 receptor inhibitors: insights on pharmacokinetic and pharmacodynamic properties.

摘要: The P2Y12 receptor is a key player in platelet activation and represents an effective pharmacological target for the inhibition of aggregation prevention atherothrombotic events. Indeed, clinical use inhibitor clopidogrel strategy inhibiting activity patients with acute coronary syndrome, preventing thrombotic events those undergoing percutaneous intervention stenting. However, has several drawbacks, which include delayed onset action, large inter-individual variability response, genetic polymorphism metabolizing enzyme, drug–drug interactions (DDIs), two-step process catalyzed by series cytochrome P450 (CYP) isoenzymes. For these reasons, new inhibitors have been developed attempt to improve on profile clopidogrel. Three inhibitors—prasugrel, cangrelor, ticagrelor—have arrived, more are coming into use. Each antagonists individual properties and, according their mechanism inhibition, can be divided irreversible (prasugrel) reversible (ticagrelor, cangrelor). These agents also different metabolic pathways: prasugrel prodrug that requires through cytochrome-dependent pathway, while ticagrelor cangrelor do not require conversion. CYP3A4 substrate/inhibitor thus it involved DDIs. significantly increases plasma levels substrates such as statins. Moreover, concomitant strong (such ketoconazole, itraconazole, clarithromycin, ritonavir, telithromycin, etc.) contraindicated, co-administration potent CYP3A inducers (carbamazepine, rifampicin, phenytoin, phenobarbital) discouraged. Prasugrel determine faster, greater, consistent adenosine diphosphate (ADP)-receptor than clopidogrel, near complete between 1–2 h after administration oral loading dose, shows rapid inhibitory effect intravenous infusion. Thus, pharmacokinetic pharmacodynamic characteristics enable clinicians personalize therapy patient-specific medical requirements better In present review, we describe properties, differences, efficacy currently available inhibitors.