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

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. 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. 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. In bleeding trauma patients, intramuscular TXA is well tolerated and rapidly absorbed. 2019-000898-23 (EudraCT); NCT03875937 (ClinicalTrials.gov).