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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...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10057831 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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