Clinical pharmacology of selatogrel for self-administration by patients with suspected acute myocardial infarction.

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.

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.

Subcutaneous Selatogrel Inhibits Platelet Aggregation in Patients With Acute Myocardial Infarction.

Background: Oral P2Y receptor antagonists exhibit delayed onset of platelet inhibition in patients with acute myocardial infarction (AMI). Selatogrel is a potent, highly selective, and reversible P2Y receptor antagonist with a rapid onset and short duration of action.

Objectives: This study sought to assess inhibition of platelet aggregation following subcutaneous administration of selatogrel in patients with AMI.

Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes.

Aims: To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS).

Methods And Results: In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966).