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PubMed Journals Articles About "Safety, Pharmacokinetic And -Dynamic Study Of PR-15, An Inhibitor Of Platelet Adhesion" RSS

06:10 EST 23rd January 2019 | BioPortfolio

Safety, Pharmacokinetic And -Dynamic Study Of PR-15, An Inhibitor Of Platelet Adhesion PubMed articles on BioPortfolio. Our PubMed references draw on over 21 million records from the medical literature. Here you can see the latest Safety, Pharmacokinetic And -Dynamic Study Of PR-15, An Inhibitor Of Platelet Adhesion articles that have been published worldwide.

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Showing "Safety Pharmacokinetic Dynamic Study Inhibitor Platelet Adhesion" PubMed Articles 1–25 of 69,000+

Reverse correlations of collagen-dependent platelet aggregation and adhesion with GPVI shedding during storage.

Platelet receptor GPVI plays an important role in platelet firm adhesion to site of vascular injury. Receptor ligation with collagen, in company with other agonist/receptor interactions, augments inside out signaling pathways leading to platelet aggregation and thrombus formation. As GPVI expression is significantly modulated by ectodomain shedding, this study aimed to examine whether GPVI shedding functionally affects collagen-mediated platelet activation during storage. 6 PRP-platelet concentrates were su...


Amyloid precursor protein is required for in vitro platelet adhesion to amyloid peptides and potentiation of thrombus formation.

Amyloid precursor protein (APP) is the precursor of amyloid β (Aβ) peptides, whose accumulation in the brain is associated with Alzheimer's disease. APP is also expressed on the platelet surface and Aβ peptides are platelet agonists. The physiological role of APP is largely unknown. In neurons, APP acts as an adhesive receptor, facilitating integrin-mediated cell adhesion, while in platelets it regulates coagulation and venous thrombosis. In this work, we analyzed platelets from APP KO mice to investigat...

A Switch to a raltegravir containing regimen does not lower platelet reactivity in HIV-infected individuals.

Platelet hyper-reactivity and increased platelet-monocyte aggregation (PMA) are associated with increased cardiovascular risk and inflammation. In a previous cross-sectional study, individuals using a raltegravir (RAL)-based regimen were found to have reduced platelet reactivity and PMA compared to other antiretroviral regimens. Our aim was to investigate whether switching from a non-integrase inhibitor regimen to a RAL-based regimen reduces platelet reactivity or PMA.


Pharmacokinetics and pharmacokinetic/pharmacodynamic relationship of vicagrel, a novel thienopyridine P2Y inhibitor, compared with clopidogrel in healthy Chinese subjects following single oral dosing.

Vicagrel, a novel thienopyridine antiplatelet agent, is an analogue of clopidogrel in development for the treatment of acute coronary syndromes. This study investigated the pharmacokinetic properties of vicagrel after single oral dosing with a direct comparison with clopidogrel in healthy Chinese subjects in the first two phase I clinical studies. The relationship between the exposure to the active metabolite and the platelet reactivity was also assessed for vicagrel.

Neutrophil-Mediated Proteolysis of Thrombospondin-1 Promotes Platelet Adhesion and String Formation.

Thrombospondin-1 (TSP-1) is primarily expressed by platelets and endothelial cells (ECs) and rapidly released upon their activation. It functions in haemostasis as a bridging molecule in platelet aggregation, by promoting platelet adhesion to collagen and by protecting von Willebrand factor strings from degradation. In blood of patients undergoing surgery and in co-cultures of neutrophils with platelets or ECs, we observed proteolysis of the 185 kDa full-length TSP-1 to a 160-kDa isoform. We hypothesized th...

Robust estimation of hemo-dynamic parameters in traditional DCE-MRI models.

In dynamic contrast enhanced (DCE) MRI, separation of signal contributions from perfusion and leakage requires robust estimation of parameters in a pharmacokinetic model. We present and quantify the performance of a method to compute tissue hemodynamic parameters from DCE data using established pharmacokinetic models.

A phase 3b, multicenter, open-label extension study of the long-term safety of anagrelide in Japanese adults with essential thrombocythemia.

Cytoreductive therapy is used in high-risk essential thrombocythemia (ET) to reduce risk of thrombohemorrhagic complications. Anagrelide is an orally active, quinazolone-derived platelet-lowering agent approved for first-line treatment of high-risk ET in Japan. Long-term safety and efficacy data were collected from 53 Japanese high-risk ET patients (Study 308); 41 patients who completed Study 308 entered this phase 3b, open-label extension (Study 309; NCT01467661). Reductions in mean platelet counts occurre...

Pharmacokinetic and cytokine profiles of melanoma patients with dabrafenib and trametinib-induced pyrexia.

The combination of a BRAF inhibitor dabrafenib and a MEK inhibitor trametinib (CombiDT) has improved outcomes compared with chemotherapy or BRAF inhibitor monotherapy in advanced BRAF V600E/K melanoma. However, CombiDT causes a high incidence of pyrexia and treatment interruptions. Pharmacokinetic analysis may provide an explanation for the pyrexia.

Clinical Pharmacology of the Reversible and Potent P2Y Receptor Antagonist ACT-246475 After Single Subcutaneous Administration in Healthy Male Subjects.

ACT-246475 is a selective and reversible P2Y receptor antagonist inducing inhibition of platelet aggregation (IPA). A randomized, double-blind, placebo-controlled, parallel-design study was performed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating single subcutaneous doses of ACT-246475 (1, 2, 4, 8, 16, or 32 mg) in healthy male subjects (N = 8 per dose, 3:1 active:placebo ratio). Pharmacodynamic effects were assessed based on maximum platelet aggregation and...

First-in-human study of LY3039478, an Oral Notch signaling inhibitor in advanced or metastatic cancer.

Deregulated Notch signaling due to mutation or overexpression of ligands and/or receptors is implicated in various human malignancies. Gamma-secretase inhibitors inhibit Notch signaling by preventing cleavage of transmembrane domain of Notch protein. LY3039478 is a novel, potent Notch inhibitor decreases Notch signaling and its downstream biologic effects. In this first-in-human study, we report the safety, pharmacokinetic (PK) profile, pharmacodynamic effects, and antitumor activity of LY3039478 in patient...

Platelet aggregation in healthy women during normal pregnancy - a longitudinal study.

Increased platelet activation is involved in obstetric complications such as preeclampsia and intrauterine growth retardation. It is of interest to study platelet aggregation during pregnancy, since increased aggregation theoretically could be a mechanism associated with placenta-mediated complications, which possibly could be prevented by drugs inhibiting platelet aggregation. There are, however, few robust studies describing platelet aggregation during normal pregnancy. The present longitudinal study was ...

Phase I safety, pharmacokinetic and pharmacodynamic trial of BMS-599626 (AC480), an oral pan-HER receptor tyrosine kinase inhibitor, in patients with advanced solid tumors.

A safety, tolerability, and pharmacokinetic analysis of two phase I studies of multitargeted small molecule tyrosine kinase inhibitor XL647 with an intermittent and continuous dosing schedule in patients with advanced solid malignancies.

To evaluate the safety, tolerability, and pharmacokinetics of XL647 and determine the maximum tolerated dose (MTD) of oral XL647 once-daily using intermittent or continuous dosing schedules.

Expression of p53 and its mechanism in prostate cancer.

The present study aimed to investigate the expression of tumor protein p53 (p53), and its mechanism of function, in prostate cancer (PC). Small interfering RNA (siRNA) was used to interfere with p53 expression in the PC cell line, DU145. Cell viability and p53 expression were analyzed using cell counting kit-8 (CCK-8) and western blotting. The effects of p53 expression on the proliferation, migration and adhesion abilities of PC cells were analyzed using Cell Counting kit-8, Transwell and adhesion assays. C...

Effects of platelet dysfunction and platelet transfusion on outcomes in traumatic brain injury patients.

Platelet inhibition in traumatic brain injury (TBI) may be due to injury or antiplatelet medication use pre-injury. This study aims to identify factors associated with increased platelet arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition and determine if platelet transfusion reduces platelet dysfunction and affects outcome.

Model-based pharmacokinetic and pharmacodynamic analysis for acute effects of a small molecule inhibitor of diacylglycerol acyltransferase-1 in the TallyHo/JngJ polygenic mouse.

The purpose of this study was to evaluate the acute effect of a small molecule inhibitor of DGAT-1 on triglycerides and cholesterol in polygenic type 2 diabetic TallyHo/JngJ (TH) mice. PF-04620110, a potent and selective DGAT-1 inhibitor, was used as a model compound in this study and which was administered to TH and ICR mice. The concentration of the model compound that produced 50% of maximum lowering of triglyceride level (IC) in TH mice was not significantly different from that in ICR mice, when estimat...

Ability of Platelet-Derived Extracellular Vesicles to Promote Neutrophil-Endothelial Cell Interactions.

We tested the ability of platelet-derived extracellular vesicles (PEV) to promote adhesion of flowing neutrophils to endothelial cells (EC). PEV were collected from platelets stimulated with collagen-related peptide, and differential centrifugation was used to collect larger vesicles enriched for platelet membrane microvesicles (PMV) or smaller vesicles enriched for platelet exosomes (Pexo). Vesicle binding and resultant activation of neutrophils and EC were assessed by flow cytometry. Flow-based adhesion a...

Population Pharmacokinetic/Pharmacodynamic Analyses of Avatrombopag in Patients With Chronic Liver Disease and Optimal Dose Adjustment Guide With Concomitantly Administered CYP3A and CYP2C9 Inhibitors.

Avatrombopag, a c-Mpl agonist, has been developed to provide an alternative therapy to standard platelet transfusion care for the treatment of thrombocytopenia. The main objectives of this article were to describe the pharmacokinetics (PK) of avatrombopag, to characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship between plasma avatrombopag concentrations and platelet count, and to identify potential intrinsic and extrinsic factors affecting PK or PK/PD in patients with chronic liver disease ...

Transversus Abdominal Plane Block in Children: Efficacy and Safety: A Randomized Clinical Study and Pharmacokinetic Profile.

The transversus abdominis plane (TAP) block has become a common regional anesthesia technique for pain management in a wide variety of abdominal procedures. Evidence to support any particular local anesthetic regimen as well as pharmacokinetic and systemic toxicity risks of TAP block remain insufficiently studied in children. The aim of this study was to compare the analgesic effects and investigate pharmacokinetic profile of levobupivacaine after ultrasound-guided TAP block using a low volume/high concentr...

Platelet Signaling in Primary Haemostasis and Arterial Thrombus Formation: Part 1.

Platelets react immediately in response to traumatic vascular injury by adhesion, activation, aggregation and subsequent haemostatic plug formation. While this reaction pattern is essential for haemostasis, platelet responses can also cause occlusive thrombi in diseased arteries, leading to myocardial infarction or stroke. Initially, flowing platelets are captured from the circulation to vascular lesions. This step is mediated by glycoprotein (GP) Ib-IX-V interacting with immobilized von Willebrand factor (...

A validated UPLC-MS/MS method for pharmacokinetic study of inflachromene, a novel microglia inhibitor.

Inflachromene (ICM), a novel microglia inhibitor, is under development to treat neuroinflammatory disorders. For the pharmacokinetic evaluation of ICM, we developed quantitative ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method in rat plasma. Protein precipitation method with acetonitrile (ACN) was used for plasma sample preparation. The analyte and carbamazepine (the internal standard) were separated by the chromatography on an ACQUITY UPLC™ BEH C18 column ru...

Safety, Tolerability, and Pharmacokinetics of Single and Repeat Doses of Nemiralisib Administered via the Ellipta Dry Powder Inhaler to Healthy Subjects.

Novel therapies to treat chronic obstructive pulmonary disease are highly desirable. The safety, tolerability, and pharmacokinetic (PK) parameters of nemiralisib, a phosphoinositide 3-kinase δ inhibitor, administered via the Ellipta dry powder inhaler (GlaxoSmithKline, Research Triangle Park, North Carolina) was evaluated, including an assessment of oral bioavailability.

EW-7197, an oral transforming growth factor β type I receptor kinase inhibitor, for preventing peritoneal adhesion formation in a rat model.

EW-7197 is an oral transforming growth factor β type I receptor kinase inhibitor currently undergoing phase I clinical trials for cancer treatment in the United States. This study evaluates whether EW-7197 prevents peritoneal adhesion formation in a rat model.

PHARMACOKINETIC STUDY OF CONVERSION BETWEEN TWO FORMULATIONS OF ONCE-DAILY EXTENDED-RELEASE TACROLIMUS IN STABLE LUNG TRANSPLANT PATIENTS.

The aim of this study was to compare the pharmacokinetic profile, tolerability, and safety of a novel once-daily extended-release formulation of tacrolimus (LCPT) with that of once-daily prolonged-release tacrolimus (ODT) in stable adult lung transplant (LT) recipients.

The HIV protease inhibitor, ritonavir, dysregulates human platelet function in vitro.

There are 37 million people globally infected with the Human Immunodeficiency Virus (HIV). People living with HIV can achieve nearly normal lifespans due to the use of antiretroviral drugs (ARVs). However, people living with HIV experience chronic inflammation and increased risk for cardiovascular diseases (CVD) relative to uninfected people. While the cause for this risk is unclear, some ARVs have been associated with CVD, and it is speculated that some ARVs potentiate inflammation in infected individuals....


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