ArticleFrontiers in pharmacology2016
The Toxicokinetic Profile of Dex40-GTMAC3-a Novel Polysaccharide Candidate for Reversal of Unfractionated Heparin.
Article in Frontiers in pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
7 citing papers in PubMed, 21 citations in OpenAlex.
- External Trigger Free Charge Switchable Cationic Ligands in the Design of Safe and Effective Universal Heparin Antidote.Advanced healthcare materials · 2024Article
- The methods for removal of direct oral anticoagulants and heparins to improve the monitoring of hemostasis: a narrative literature review.Thrombosis journal · 2023Review
- Reversal Activity and Toxicity of Heparin-Binding Copolymer after Subcutaneous Administration of Enoxaparin in Mice.International journal of molecular sciences · 2021Article
- In vitro and in vivo safety studies indicate that R15, a synthetic polyarginine peptide, could safely reverse the effects of unfractionated heparin.FEBS open bio · 2021Article
- Cardiovascular and Respiratory Toxicity of Protamine Sulfate in Zebrafish and Rodent Models.Pharmaceutics · 2021Article
- The Inhibitory Effect of Protamine on Platelets is Attenuated by Heparin without Inducing Thrombocytopenia in Rodents.Marine drugs · 2019Article
- Approaches to prevent bleeding associated with anticoagulants: current status and recent developments.Drug delivery and translational research · 2018Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Though protamine sulfate is the only approved antidote of unfractionated heparin (UFH), yet may produce life threatening side effects such as systemic hypotension, catastrophic pulmonary vasoconstriction or allergic reactions. We have described 40 kDa dextrans (Dex40) substituted with glycidyltrimethylammonium chloride (GTMAC) as effective, immunogenically and hemodynamically neutral inhibitors of UFH. The aim of the present study was to evaluate in mice and rats toxicokinetic profile of the most promising polymer-Dex40-GTMAC3. Polymer was rapidly eliminated with a half-time of 12.5 ± 3.0 min in Wistar rats, and was mainly distributed to the kidneys and liver in mice. The safety studies included the measurement of blood count and blood biochemistry, erythrocyte osmotic fragility and the evaluation of the histological alterations in kidneys, liver and lungs of mice and rats in acute and chronic experiments. We found that Dex40-GTMAC3 is not only effective but also very well tolerated. Additionally, we found that protamine may cause overt hemolysis with appearance of permanent changes in the liver and kidneys. In summary, fast renal clearance behavior and generally low tissue accumulation of Dex40-GTMAC3 is likely to contribute to its superior to protamine biocompatibility. Intravenous administration of therapeutic doses to living animals does not result in the immunogenic, hemodynamic, blood, and organ toxicity. Dex40-GTMAC3 seems to be a promising effective and safe candidate for further clinical development as new UFH reversal agent.
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