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Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: a clinical trial.

Grassin-Delyle, S; Shakur-Still, H; Picetti, R; Frimley, L; Jarman, H; Davenport, R; McGuinness, W; Moss, P; Pott, J; Tai, N; et al. Grassin-Delyle, S; Shakur-Still, H; Picetti, R; Frimley, L; Jarman, H; Davenport, R; McGuinness, W; Moss, P; Pott, J; Tai, N; Lamy, E; Urien, S; Prowse, D; Thayne, A; Gilliam, C; Pynn, H; Roberts, I (2021) Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: a clinical trial. Br J Anaesth, 126 (1). pp. 201-209. ISSN 1471-6771 https://doi.org/10.1016/j.bja.2020.07.058
SGUL Authors: Moss, Philip Simon

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Abstract

BACKGROUND: Intravenous 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. METHODS: We 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. RESULTS: Intramuscular 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. CONCLUSIONS: In bleeding trauma patients, intramuscular TXA is well tolerated and rapidly absorbed. CLINICAL TRIAL REGISTRATION: 2019-000898-23 (EudraCT); NCT03875937 (ClinicalTrials.gov).

Item Type: Article
Additional Information: © 2020 The Author(s). Published by Elsevier Ltd on behalf of British Journal of Anaesthesia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: antifibrinolytic, clinical trial, haemorrhage, intramuscular, tranexamic acid, trauma, Anesthesiology, 1103 Clinical Sciences
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Clinical Education (INMECE )
Journal or Publication Title: Br J Anaesth
ISSN: 1471-6771
Language: eng
Dates:
DateEvent
January 2021Published
30 September 2020Published Online
24 July 2020Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
EPPHZQ25London School of Hygiene and Tropical MedicineUNSPECIFIED
PubMed ID: 33010927
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/112502
Publisher's version: https://doi.org/10.1016/j.bja.2020.07.058

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