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Role of the P2Y12 receptor on thrombus formation and evolution in therapeutic strategies.
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Clinical pharmacology of selatogrel for self-administration by patients with suspected acute myocardial infarction.
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Department of Clinical Pharmacology, Idorsia Pharmaceuticals, Allschwil, Switzerland.
Introduction: P2Y12 receptor antagonists (P2Y12 inhibitors) are well established for the treatment of coronary artery disease. The P2Y12 inhibitors currently commercially available present either pharmacokinetic limitations (due to delayed absorption, bioactivation requirement via CYP enzymes, or need of intravenous administration), pharmacodynamic (PD) limitations (limited % inhibition of platelet aggregation (IPA) or relevant PD interactions) or safety limitations (major bleeding in specific populations).
Areas Covered: Selatogrel, a 2-phenylpyrimidine-4-carboxamide analog, is a potent, reversible, and selective P2Y12 inhibitor administered subcutaneously that is under development for the treatment of acute myocardial infarction (AMI) in patients with a recent history of AMI.
Mind the Gap: Model-Based Switching from Selatogrel to Maintenance Therapy with Oral P2Y12 Receptor Antagonists.
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Department of Clinical Pharmacology, Idorsia Pharmaceuticals Ltd., 4123 Allschwil, Switzerland.
The P2Y receptor antagonist selatogrel is being developed for subcutaneous self-administration with a ready-to-use autoinjector at the onset of acute myocardial infarction (AMI) symptoms. The unique pharmacological profile of selatogrel (fast, potent, and short-acting) can bridge the time gap between the onset of AMI and first medical care. A clinical Phase 1 study showed a time-dependent pharmacodynamic interaction between selatogrel and loading doses of clopidogrel and prasugrel.
View Article and Find Full Text PDFComparison of the effects of the GPIIb-IIIa antagonist Zalunfiban and the P2Y12 antagonist Selatogrel on Platelet Aggregation.
J Thromb Thrombolysis
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MLM Medical Labs, 140 Collins Street, Memphis, TN, 38117, USA.
Understanding the pharmacodynamic effects of platelet inhibitors is standard for developing more effective antithrombotic therapies. An example is the antithrombotic treatment of acute coronary syndrome (ACS), in particular ST-elevated myocardial infarction (STEMI) patients who are in need for rapid acting strong antithrombotic therapy despite the use of aspirin and oral P2Y12-inhibitors. In this study, we evaluated two injectable platelet inhibitors under clinical development (the P2Y12 antagonist selatogrel and the GPIIb-IIIa antagonist zalunfiban) that may be amenable to pre-hospital treatment of STEMI patients.
View Article and Find Full Text PDFDual Antiplatelet Therapy with Parenteral P2Y Inhibitors: Rationale, Evidence, and Future Directions.
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Department of Clinical and Experimental Medicine, University of Messina, 98124 Messina, Italy.
Dual antiplatelet therapy (DAPT), consisting of the combination of aspirin and an inhibitor of the platelet P2Y receptor for ADP, remains among the most investigated treatments in cardiovascular medicine. While a substantial amount of research initially stemmed from the observations of late and very late stent thrombosis events in the first-generation drug-eluting stent (DES) era, DAPT has been recently transitioning from a purely stent-related to a more systemic secondary prevention strategy. Oral and parenteral platelet P2Y inhibitors are currently available for clinical use.
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