• Stanislas Grassin-Delyle, Haleema Shakur-Still, Roberto Picetti, Lauren Frimley, Heather Jarman, Ross Davenport, William McGuinness, Phil Moss, Jason Pott, Nigel Tai, Elodie Lamy, Saïk Urien, Danielle Prowse, Andrew Thayne, Catherine Gilliam, Harvey Pynn, and Ian Roberts.
• Département de Biotechnologie de la Santé, Université Paris-Saclay, UVSQ, Inserm, Infection et inflammation, Montigny le Bretonneux, France; Département des Maladies des Voies Respiratoires, Hôpital Foch, Suresnes, France.
• Br J Anaesth. 2021 Jan 1; 126 (1): 201-209.

BackgroundIntravenous tranexamic acid (TXA) reduces bleeding deaths after injury and childbirth. It is most effective when given early. In many countries, pre-hospital care is provided by people who cannot give i.v. injections. We examined the pharmacokinetics of intramuscular TXA in bleeding trauma patients.MethodsWe conducted an open-label pharmacokinetic study in two UK hospitals. Thirty bleeding trauma patients received a loading dose of TXA 1 g i.v., as per guidelines. The second TXA dose was given as two 5 ml (0·5 g each) i.m. injections. We collected blood at intervals and monitored injection sites. We measured TXA concentrations using liquid chromatography coupled to mass spectrometry. We assessed the concentration time course using non-linear mixed-effect models with age, sex, ethnicity, body weight, type of injury, signs of shock, and glomerular filtration rate as possible covariates.ResultsIntramuscular TXA was well tolerated with only mild injection site reactions. A two-compartment open model with first-order absorption and elimination best described the data. For a 70-kg patient, aged 44 yr without signs of shock, the population estimates were 1.94 h-1 for i.m. absorption constant, 0.77 for i.m. bioavailability, 7.1 L h-1 for elimination clearance, 11.7 L h-1 for inter-compartmental clearance, 16.1 L volume of central compartment, and 9.4 L volume of the peripheral compartment. The time to reach therapeutic concentrations (5 or 10 mg L-1) after a single intramuscular TXA 1 g injection are 4 or 11 min, with the time above these concentrations being 10 or 5.6 h, respectively.ConclusionsIn bleeding trauma patients, intramuscular TXA is well tolerated and rapidly absorbed.Clinical Trial Registration2019-000898-23 (EudraCT); NCT03875937 (ClinicalTrials.gov).Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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