Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects.

Background And Objectives: Daridorexant, a dual orexin receptor antagonist was recently approved for the treatment of insomnia at doses up to 50 mg once per night. This study investigated the effect of single-dose and multiple-dose daridorexant 50 mg at steady state on the pharmacokinetics (PK) of the cytochrome P450 (CYP) 3A4-sensitive substrate midazolam, and the effect of single-dose daridorexant 50 mg on the PK and pharmacodynamics (PD) of the CYP2C9-sensitive substrate warfarin.

Methods: In this prospective, single-center, open-label, fixed-sequence, phase I, drug-drug interaction study, 18 healthy male subjects sequentially received Treatment A, B, and C in three periods.

The Neurocognitive Bases of Meaningful Intransitive Gestures: A Systematic Review and Meta-analysis of Neuropsychological Studies.

Researchers and clinicians have long used meaningful intransitive (i.e., not tool-related; MFI) gestures to assess apraxia-a complex and frequent motor-cognitive disorder.

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.

Pharmacokinetics, pharmacodynamics and safety of the novel C-X-C chemokine receptor 3 antagonist ACT-777991: Results from the first-in-human study in healthy adults.

Aims: The C-X-C chemokine receptor 3 (CXCR3) axis is highly upregulated in the tissue of patients with type 1 diabetes. Antagonizing CXCR3 may reduce the migration of CXCR3-expressing cells to the pancreas. The pharmacokinetics (PKs), target engagement (TE) (inhibition of CXCR3 internalization) and safety of single- and multiple-ascending doses (SADs and MADs) of ACT-777991, a novel orally available potent CXCR3 antagonist, were assessed in a double-blind, randomized, placebo-controlled phase 1 study.