Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction

Bor, W L; Zheng, Kai; Tavenier, Anne H.; Gibson, C. Michael; Granger, Christopher B.; Bentur, Ohad S.; Lobatto, Rita; Postma, Sonja; Coller, Barry S.; Hof, Arnoud W J van 't; Berg, Jürrien M. ten

doi:10.4244/eij-d-21-00287

Cited by 26 publications

(19 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Development of effective and safe reversal compounds for antiplatelet agents is also an area of unmet need. Moreover, novel antiplatelet drugs are in the pipeline (among which RUC-4, selatogrel, revacept, glenzocimab; non-exhaustive list) (199)(200)(201)(202)(203). How these potential new therapeutics will fit within the current paradigm of antiplatelet therapy and whether they will lead to safer combinations in the clinical practice remain to be determined.…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet Therapy for Atherothrombotic Disease in 2022—From Population to Patient-Centered Approaches

Jourdi

Godiér

Lordkipanidzé

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Antiplatelet agents, with aspirin and P2Y12 receptor antagonists as major key molecules, are currently the cornerstone of pharmacological treatment of atherothrombotic events including a variety of cardio- and cerebro-vascular as well as peripheral artery diseases. Over the last decades, significant changes have been made to antiplatelet therapeutic and prophylactic strategies. The shift from a population-based approach to patient-centered precision medicine requires greater awareness of individual risks and benefits associated with the different antiplatelet strategies, so that the right patient gets the right therapy at the right time. In this review, we present the currently available antiplatelet agents, outline different management strategies, particularly in case of bleeding or in perioperative setting, and develop the concept of high on-treatment platelet reactivity and the steps toward person-centered precision medicine aiming to optimize patient care.

show abstract

Section: Discussionmentioning

confidence: 99%

Antiplatelet Therapy for Atherothrombotic Disease in 2022—From Population to Patient-Centered Approaches

Jourdi

Godiér

Lordkipanidzé

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

show abstract

“…All three agents are characterized by fast onset -and short duration-of high-grade platelet inhibition, with the GPI having broader inhibitory effects on platelet function than P2Y 12 inhibitors. 43,52,58 The pharmacodynamic profiles of cangrelor and zalunfiban make these drugs particularly promising with regards to safety as the antiplatelet effects of these drugs wear off roughly at the time when oral P2Y 12 inhibitors become effective, thereby decreasing hemorrhagic risk and allowing for emergency cardiac surgery when indicated. 52,57 Also, the risk of GPI-induced thrombocytopenia by zalunfiban is expected to be lower or absent when compared with currently available GPIs, given the molecular mechanism responsible for locking the GPIIb/IIIa receptor.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, a phase IIa open-label clinical study was conducted in 27 STEMI patients (mean age: 62 years) to assess the tolerability, pharmacodynamics, and pharmacokinetics of even higher escalating, weight-adjusted doses of subcutaneous zalunfiban. 52 The primary pharmacodynamic endpoint was defined as !77% or greater inhibition of iso-thrombin receptor activating peptide (iso-TRAP)-induced platelet aggregation measured at 15 minutes after zalunfiban administration in the cardiac catheterization laboratory with the VerifyNow assay. In comparison, 77% inhibition after stimulation with 3 to 4 µmol/L iso-TRAP corresponds to approximately 80% inhibition with LTA stimulated by 20 µmol/L ADP, the value that has been most closely correlated with antithrombotic effects in vivo using other GPIs.…”

Section: Parenteral Agents Under Clinical Development Zalunfibanmentioning

confidence: 99%

Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions

et al. 2022

View full text Add to dashboard Cite

Oral inhibitors of the platelet P2Y12 receptor are indispensable in the treatment of ST-elevation myocardial infarction (STEMI), improving outcomes and even reducing mortality in some studies. However, these drugs are limited by delayed absorption and suboptimal platelet inhibition at the time of primary percutaneous coronary intervention. Despite efforts to achieve faster and more sustained platelet inhibition, strategies such as prehospital administration, higher loading doses, and crushed formulations have not led to improved coronary reperfusion. Parenteral glycoprotein IIb/IIIa inhibitors act sooner and are more potent than oral P2Y12 inhibitors, but their use has been limited by the increased risk of major bleeding and thrombocytopenia. Hence, there is a clinical need to refine drugs that deliver rapid, effective, yet safe platelet inhibition in the setting of STEMI. Novel parenteral antiplatelet drugs, such as cangrelor, selatogrel, and zalunfiban, have been recently developed to achieve rapid, potent antiplatelet effects while preserving hemostasis. We provide a description of currently available parenteral antiplatelet agents and of those in clinical development for prehospital administration in STEMI patients.

show abstract

“…The drug had excellent tolerability up to doses of 0.075 mg/kg in healthy volunteers and patients with stable CAD. A recent study has published data from an open-label, dose escalating, and phase 2 study of a weight-adjusted dose of RUC-4 in 27 patients with STEMI [ 75 ]. A single S/C dose of the drug (at different doses of 0.075, 0.090, and 0.110 mg/kg) resulted in high-grade inhibition of platelet function within 15 min.…”

Section: Future Directionsmentioning

confidence: 99%

Ideal P2Y12 Inhibitor in Acute Coronary Syndrome: A Review and Current Status

Pradhan

Tiwari

Caminiti

et al. 2022

IJERPH

View full text Add to dashboard Cite

Dual antiplatelet therapy (DAPT) has remained a cornerstone for management of acute coronary syndrome (ACS) over the years. Clopidogrel has been the quintessential P2Y12 receptor (platelet receptor for Adenosine 5′ diphosphate) inhibitor for the past two decades. With the demonstration of unequivocal superior efficacy of prasugrel/ticagrelor over clopidogrel, guidelines now recommend these agents in priority over clopidogrel in current management of ACS. Cangrelor has revived the interest in injectable antiplatelet therapy too. Albeit the increased efficacy of these newer agents comes at the cost of increased bleeding and this becomes more of a concern when combined with aspirin. Which P2Y12i is superior over another has been intensely debated over last few years after the ISAR-REACT 5 study with inconclusive data. Three novel antiplatelet agents are already in the pipeline of ACS with all of them succeeding in phase II studies. The search for an ideal antiplatelet remains a need of the hour for optimal reduction of ischemic events in ACS.

show abstract

Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction

Cited by 26 publications

References 31 publications

Antiplatelet Therapy for Atherothrombotic Disease in 2022—From Population to Patient-Centered Approaches

Antiplatelet Therapy for Atherothrombotic Disease in 2022—From Population to Patient-Centered Approaches

Parenteral Antiplatelet Drugs in ST-Elevation Myocardial Infarction: Current Status and Future Directions

Ideal P2Y12 Inhibitor in Acute Coronary Syndrome: A Review and Current Status

Contact Info

Product

Resources

About