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

Stanislas Grassin-Delyle; Haleema Shakur-Still ORCID logo; Roberto Picetti ORCID logo; Lauren Frimley; Heather Jarman; Ross Davenport; William McGuinness; Phil Moss; Jason Pott; Nigel Tai; +7 more... Elodie Lamy; Saïk Urien; Danielle Prowse; Andrew Thayne; Catherine Gilliam; Harvey Pynn; Ian Roberts ORCID logo; (2020) Pharmacokinetics of intramuscular tranexamic acid in bleeding trauma patients: a clinical trial. British journal of anaesthesia, 126 (1). pp. 201-209. ISSN 0007-0912 DOI: 10.1016/j.bja.2020.07.058
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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).


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