Arik Eisenkraft, Linn Wagnert-Avraham, Rotem Azmon, Michael Tabi, Elon Glassberg, Yoav Mintz, Suhair Abdeen, Muhammad Abdel-Haq, Abraham Domb, Dean Nachman, S David Gurtz
{"title":"基于自体注射器给药的氨甲环酸在不受控制的出血猪模型中提供了药代动力学效果。","authors":"Arik Eisenkraft, Linn Wagnert-Avraham, Rotem Azmon, Michael Tabi, Elon Glassberg, Yoav Mintz, Suhair Abdeen, Muhammad Abdel-Haq, Abraham Domb, Dean Nachman, S David Gurtz","doi":"10.1016/j.injury.2025.112721","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hemorrhage remains the principal cause of death on the battlefield. It is suggested that Tranexamic acid (TXA) can improve survival of severely-bleeding casualties. The intravenous approach is not always available in the pre-hospital setting. It was shown that for every 15 min delay, the efficiency of TXA decreases by 10 %. This study was designed to assess the pharmacokinetic, pharmacodynamic, and pre-clinical efficacy of a TXA autoinjector in uncontrolled hemorrhage in swine.</p><p><strong>Methods: </strong>Non-compressible hemorrhage was induced by laparoscopic partial liver resection. TXA was administered intramuscularly by autoinjector (n = 25) or intravenously (control, n = 5). Blood levels of TXA and dynamics of clot formation were determined. Euthanasia was performed ninety minutes after injury followed by a laparotomy for the measurement of free blood and clots in the abdomen.</p><p><strong>Results: </strong>The TXA levels in the autoinjector group exceeded the effective therapeutic threshold within <5 min and remained above the 10 mg/L threshold throughout the experiment. Intra-abdominal blood volumes, hemodynamic parameters, and indices of clot formation were similar between autoinjector-delivered and intravenouslyadministered groups.</p><p><strong>Conclusions: </strong>Autoinjector-based TXA provides sustained, anti-fibrinolytic levels within 2-5 min of administration in a swine model of uncontrolled hemorrhage emphasizing its important.</p>","PeriodicalId":94042,"journal":{"name":"Injury","volume":" ","pages":"112721"},"PeriodicalIF":2.0000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Autoinjector-based delivery of tranexamic acid provides pharmacokinetic efficacy in a porcine model of uncontrolled hemorrhage.\",\"authors\":\"Arik Eisenkraft, Linn Wagnert-Avraham, Rotem Azmon, Michael Tabi, Elon Glassberg, Yoav Mintz, Suhair Abdeen, Muhammad Abdel-Haq, Abraham Domb, Dean Nachman, S David Gurtz\",\"doi\":\"10.1016/j.injury.2025.112721\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Hemorrhage remains the principal cause of death on the battlefield. It is suggested that Tranexamic acid (TXA) can improve survival of severely-bleeding casualties. The intravenous approach is not always available in the pre-hospital setting. It was shown that for every 15 min delay, the efficiency of TXA decreases by 10 %. This study was designed to assess the pharmacokinetic, pharmacodynamic, and pre-clinical efficacy of a TXA autoinjector in uncontrolled hemorrhage in swine.</p><p><strong>Methods: </strong>Non-compressible hemorrhage was induced by laparoscopic partial liver resection. TXA was administered intramuscularly by autoinjector (n = 25) or intravenously (control, n = 5). Blood levels of TXA and dynamics of clot formation were determined. Euthanasia was performed ninety minutes after injury followed by a laparotomy for the measurement of free blood and clots in the abdomen.</p><p><strong>Results: </strong>The TXA levels in the autoinjector group exceeded the effective therapeutic threshold within <5 min and remained above the 10 mg/L threshold throughout the experiment. Intra-abdominal blood volumes, hemodynamic parameters, and indices of clot formation were similar between autoinjector-delivered and intravenouslyadministered groups.</p><p><strong>Conclusions: </strong>Autoinjector-based TXA provides sustained, anti-fibrinolytic levels within 2-5 min of administration in a swine model of uncontrolled hemorrhage emphasizing its important.</p>\",\"PeriodicalId\":94042,\"journal\":{\"name\":\"Injury\",\"volume\":\" \",\"pages\":\"112721\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2025-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Injury\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1016/j.injury.2025.112721\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Injury","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.injury.2025.112721","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Autoinjector-based delivery of tranexamic acid provides pharmacokinetic efficacy in a porcine model of uncontrolled hemorrhage.
Background: Hemorrhage remains the principal cause of death on the battlefield. It is suggested that Tranexamic acid (TXA) can improve survival of severely-bleeding casualties. The intravenous approach is not always available in the pre-hospital setting. It was shown that for every 15 min delay, the efficiency of TXA decreases by 10 %. This study was designed to assess the pharmacokinetic, pharmacodynamic, and pre-clinical efficacy of a TXA autoinjector in uncontrolled hemorrhage in swine.
Methods: Non-compressible hemorrhage was induced by laparoscopic partial liver resection. TXA was administered intramuscularly by autoinjector (n = 25) or intravenously (control, n = 5). Blood levels of TXA and dynamics of clot formation were determined. Euthanasia was performed ninety minutes after injury followed by a laparotomy for the measurement of free blood and clots in the abdomen.
Results: The TXA levels in the autoinjector group exceeded the effective therapeutic threshold within <5 min and remained above the 10 mg/L threshold throughout the experiment. Intra-abdominal blood volumes, hemodynamic parameters, and indices of clot formation were similar between autoinjector-delivered and intravenouslyadministered groups.
Conclusions: Autoinjector-based TXA provides sustained, anti-fibrinolytic levels within 2-5 min of administration in a swine model of uncontrolled hemorrhage emphasizing its important.