Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis. (7th February 2018) - Grassin‐Delyle, S.
Summary: Tranexamic acid is used both pre‐hospital and in‐hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre‐hospital anti‐hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy‐three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre‐hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography‐mass spectrometry, and modelled the data using non‐linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30–55 [5–135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43–70 [20–148]) min after pre‐hospital administration of the drug. The measured concentration was 28.7 (21.5–38.5 [8.7–89.0]) μg.ml −1 . Our subjects had sustained severe trauma; injury severity score 20 (16–29 [5–75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two‐compartment open model with body‐weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre‐hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations.