Transition from Syringe to Autoinjector Based on Bridging Pharmacokinetics and Pharmacodynamics of the P2Y12 Receptor Antagonist Selatogrel in Healthy Subjects

2021 ◽  
Author(s):  
Isabelle Zenklusen ◽  
Chih-Hsuan Hsin ◽  
Uta Schilling ◽  
Martin Kankam ◽  
Andreas Krause ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Healthy Subjects ◽  
P2y12 Receptor ◽  
Pharmacokinetics And Pharmacodynamics ◽  
P2y12 Receptor Antagonist

Absorption, distribution, metabolism and excretion of the P2Y12 receptor antagonist selatogrel after subcutaneous administration in healthy subjects

Xenobiotica ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 427-434 ◽  
Author(s):  
Mike Ufer ◽  
Christine Huynh ◽  
Jan Jaap van Lier ◽  
Eva Caroff ◽  
Hartmut Fischer ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Healthy Subjects ◽  
Subcutaneous Administration ◽  
P2y12 Receptor ◽  
P2y12 Receptor Antagonist

Pharmacokinetics and Pharmacodynamics of a Bolus and Infusion of Cangrelor: A Direct, Parenteral P2Y12 Receptor Antagonist

2010 ◽  
Vol 50 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Wendell S. Akers ◽  
Jennifer J. Oh ◽  
Julie H. Oestreich ◽  
Suellen Ferraris ◽  
Mary Wethington ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
P2y12 Receptor ◽  
Pharmacokinetics And Pharmacodynamics ◽  
P2y12 Receptor Antagonist

A New Reversible and Potent P2Y12 Receptor Antagonist (ACT-246475): Tolerability, Pharmacokinetics, and Pharmacodynamics in a First-in-Man Trial

2014 ◽  
Vol 34 (11) ◽  
pp. 807-818 ◽  
Author(s):  
Daniela Baldoni ◽  
Shirin Bruderer ◽  
Andreas Krause ◽  
Marcello Gutierrez ◽  
Pierre Gueret ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
P2y12 Receptor ◽  
Pharmacokinetics And Pharmacodynamics ◽  
P2y12 Receptor Antagonist

Clopidogrel (plavix), a P2Y12 receptor antagonist, inhibits bone cell function in vitro and decreases trabecular bone in vivo

Bone ◽  
2012 ◽  
Vol 50 ◽  
pp. S45
Author(s):  
S. Syberg ◽  
A. Brandao-Burch ◽  
J.J. Patel ◽  
M.O. Hajjawi ◽  
T.R. Arnett ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Trabecular Bone ◽  
Cell Function ◽  
Bone Cell ◽  
P2y12 Receptor ◽  
P2y12 Receptor Antagonist

Prasugrel Aggravates the Inflammatory Response in a PG-PS-Induce Arthritis Model,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3268-3268
Author(s):  
Analia E Garcia ◽  
Mario C Rico ◽  
Elisabetta Liverani ◽  
Satya P. Kunapuli ◽  
Raul A. De La Cadena
Keyword(s):  
Receptor Antagonist ◽  
Plasma Levels ◽  
Conflicts Of Interest ◽  
Inflammatory Diseases ◽  
Additional Treatment ◽  
P2y12 Receptor ◽  
Platelet Factor ◽  
Arthritis Model ◽  
P2y12 Receptor Antagonist ◽  
Inflammatory Changes

Abstract Abstract 3268 Prasugrel is a very potent and effective P2Y12 receptor antagonist, used primarily to prevent thrombotic events in patients managed for percutaneous coronary intervention (PCI). It is not recommended as prophylaxis antithrombotic therapy because prasugrel increases patient's risk of bleeding. Even though indication of prasugrel treatment has been limited to the PCI procedure, there are not reports of the effects of prasugrel in patients with associated inflammatory diseases that undergo for PCI. Thus, we evaluate the effects of prasugrel, for 21 days, in a peptidoglycan polysaccharide (PG-PS)-induced arthritis rat model. Lewis rats were randomly separated into four groups from which only half of the animals were induced with PG-PS. There was a significant increase in the inflammatory changes observed in the PG-PS-induced animals treated with prasugrel compared to the PG-PS-induced control including a) increase joint diameter associated with visible signs of inflammation (during days 4 to 6 [p<0.05] and days 13 to 21 [p<0.001]); b) microscopic studies of hind joints showed marked increase in histomorphometric measurements including leukocyte infiltration, synoviocyte hyperplasia, fibrosis and neovascularization (significant increase in vessel number and size); and c) significant increase in platelet count (1,047 ± 89.03 × 103 vs. 710.8 ± 52.65 × 103, p<0.05). Platelet factor 4 (PF4) plasma levels were increased in PG-PS induced control as well as in PG-PS treated with prasugrel animals, however no significant differences were observed between these two groups. Plasma levels of cytokines such as IL-1 beta, IL-6, MIP1 alpha, MCP1, and RANTES were increased in PG-PS-induced animals (both, control and prasugrel treated animals). Only MIP1 alpha levels were significantly increased with additional treatment of prasugrel (p<0.05). In contrast, IL-10 levels were lower in the PG-PS-induced treated with prasugrel (p<0.05). In summary, treatment with P2Y12 receptor antagonist drugs, such as prasugrel, increases the inflammatory changes in PG-PS-induced arthritis model. Further investigations are in need to elucidate the potential unwanted effect of the P2Y12 receptor antagonists in patients afflicted with inflammatory illnesses. Disclosures: No relevant conflicts of interest to declare.

A novel P2Y12 adenosine diphosphate receptor antagonist that inhibits platelet aggregation and thrombus formation in rat and dog models

2007 ◽  
Vol 97 (05) ◽  
pp. 847-855 ◽  
Author(s):  
Jon Vincelette ◽  
Valdeci Cunha ◽  
Baby Martin-McNulty ◽  
Cornell Mallari ◽  
Richard Fitch ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Thrombus Formation ◽  
Therapeutic Index ◽  
Bleeding Risk ◽  
Adenosine Diphosphate ◽  
Similar Efficacy ◽  
Experimental Models ◽  
P2y12 Receptor ◽  
P2y12 Receptor Antagonist

SummaryIrreversible platelet inhibitors, such as aspirin and clopidogrel, have limited anti-thrombotic efficacy in the clinic due to their bleeding risk. We have developed an orally active reversible P2Y12 receptor antagonist, BX 667.The aim of this study was to determine if the reversible antagonist BX 667 had a greater therapeutic index than the irreversible P2Y12 receptor antagonist clopidogrel. Since BX 667 is rapidly converted to its active metabolite BX 048 in rats,we first injected BX 048 intravenously (iv) in a rat arterial venous (A-V) shunt model of thrombosis.BX 048 dose- and concentration-dependently attenuated thrombosis. When administered orally, BX 667 and clopidogrel had similar efficacy, but BX 667 caused less bleeding than clopidogrel. In a rat model of a platelet-rich thrombus induced by vessel injury with FeCl2, both BX 667 and clopidogrel exhibited higher levels of thrombus inhibition after oral administration compared to their potency in the A-V shunt model.Again, BX 667 caused less bleeding than clopidogrel. In a dog cyclic flow model, iv injection of either BX 667 or clopidogrel dose-dependently reduced thrombus formation with lower bleeding for BX 667 than clopidogrel. Inhibition of thrombosis was highly correlated with inhibition of ADP-induced platelet aggregation in these animal models. In dogs pre-treated with aspirin, BX 667 maintained its wider therapeutic index, measured by inhibition of platelet aggregation over bleeding, compared to the aspirin-clopidogrel combination.These data demonstrate that the reversible P2Y12 receptor antagonist, BX 667, has a wider therapeutic index than clopidogrel in experimental models of thrombosis.

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