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In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke

Alteplase is the only FDA-approved drug for thrombolysis in acute ischemic stroke (AIS). Meanwhile, several thrombolytic drugs are deemed to be promising candidates to substitute alteplase. This paper evaluates the efficacy and safety of urokinase, ateplase, tenecteplase, and reteplase for intraveno...

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Detalles Bibliográficos
Autores principales: Yang, Yilin, Gu, Boram, Xu, Xiao Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057831/
https://www.ncbi.nlm.nih.gov/pubmed/36986658
http://dx.doi.org/10.3390/pharmaceutics15030797
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author Yang, Yilin
Gu, Boram
Xu, Xiao Yun
author_facet Yang, Yilin
Gu, Boram
Xu, Xiao Yun
author_sort Yang, Yilin
collection PubMed
description Alteplase is the only FDA-approved drug for thrombolysis in acute ischemic stroke (AIS). Meanwhile, several thrombolytic drugs are deemed to be promising candidates to substitute alteplase. This paper evaluates the efficacy and safety of urokinase, ateplase, tenecteplase, and reteplase for intravenous AIS therapy by computational simulations of the pharmacokinetics and pharmacodynamics combined with a local fibrinolysis model. The performances of the drugs are evaluated by comparing clot lysis time, plasminogen activator inhibitor (PAI) inhibition resistance, intracranial hemorrhage (ICH) risk, and activation time from drug administration to clot lysis. Our results reveal that urokinase has the quickest lysis completion but the highest ICH risk due to excess fibrinogen depletion in systemic plasma. While tenecteplase and alteplase have very similar thrombolysis efficacy, tenecteplase has a lower risk of ICH and better resistance to PAI-1. Among the four simulated drugs, reteplase has the slowest fibrinolysis rate, but fibrinogen concentration in systemic plasma is unaffected during thrombolysis.
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spelling pubmed-100578312023-03-30 In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke Yang, Yilin Gu, Boram Xu, Xiao Yun Pharmaceutics Article Alteplase is the only FDA-approved drug for thrombolysis in acute ischemic stroke (AIS). Meanwhile, several thrombolytic drugs are deemed to be promising candidates to substitute alteplase. This paper evaluates the efficacy and safety of urokinase, ateplase, tenecteplase, and reteplase for intravenous AIS therapy by computational simulations of the pharmacokinetics and pharmacodynamics combined with a local fibrinolysis model. The performances of the drugs are evaluated by comparing clot lysis time, plasminogen activator inhibitor (PAI) inhibition resistance, intracranial hemorrhage (ICH) risk, and activation time from drug administration to clot lysis. Our results reveal that urokinase has the quickest lysis completion but the highest ICH risk due to excess fibrinogen depletion in systemic plasma. While tenecteplase and alteplase have very similar thrombolysis efficacy, tenecteplase has a lower risk of ICH and better resistance to PAI-1. Among the four simulated drugs, reteplase has the slowest fibrinolysis rate, but fibrinogen concentration in systemic plasma is unaffected during thrombolysis. MDPI 2023-02-28 /pmc/articles/PMC10057831/ /pubmed/36986658 http://dx.doi.org/10.3390/pharmaceutics15030797 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Yilin
Gu, Boram
Xu, Xiao Yun
In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke
title In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke
title_full In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke
title_fullStr In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke
title_full_unstemmed In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke
title_short In Silico Study of Different Thrombolytic Agents for Fibrinolysis in Acute Ischemic Stroke
title_sort in silico study of different thrombolytic agents for fibrinolysis in acute ischemic stroke
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10057831/
https://www.ncbi.nlm.nih.gov/pubmed/36986658
http://dx.doi.org/10.3390/pharmaceutics15030797
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