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Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis - 14/6/2018


Anaesthesia 2018; 73: 719-29

Introduction

Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients, although dosing remains empirical. These authors 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.

 

Methods

A total of 73 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 the plasma tranexamic acid concentration was measured using liquid chromatography-mass spectrometry. The data were modelled using non-linear mixed-effect modelling. Tranexamic acid was administered at a median (interquartile range [range]) time of 43 (30–55 [5–135]) minutes after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43–70 [20–148]) minutes after pre-hospital administration of the drug.

 

Results


The measured concentration was 28.7 (21.5–38.5 [8.7–89.0]) µg/ml. The subjects had sustained severe trauma, with an injury severity score of 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, the authors propose additional dosing schemes to maintain a specific target blood concentration for as long as required.

 

Conclusions


This was the first study to investigate the plasma levels and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. The authors state that their proposed dosing regimen could be used in subsequent clinical trials, in order to study efficacy and tolerance profiles with controlled blood concentrations.


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ArticleDate:20180614
SiteSection: Abstracts



 
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