Optimizing Tranexamic Acid Treatment in Trauma
Abstract
In 2013, a committee of trauma management experts formed at the request of the Office of the Assistant Secretary of Defense for Health Affairs and the Joint Program Committee for Combat Casualty Care Research to develop research priorities for TXA identified “dosing” as a research priority. Specifically, they stated “All available data are based on one dosage regimen; could other regimens improve efficacy and safety or worsen efficacy and safety? How are pharmacokinetics affected by trauma?” We aim to develop a physiologically based pharmacokinetics (PBPK) model of tranexamic acid that will have the capability of predicting the impact of alterations in physiology on the time course of medications and have the ability to extrapolate to human clinical settings. To build this model we will first determine organ and tissue blood flow after grade I- IV hemorrhage in the swine using microsphere studies and determine organ and tissue partition coefficients at steady state plasma levels of TXA in the swine. We will then develop a PBPK model of TXA that includes elimination through hemorrhage and use the newly developed PBPK model as a tool to explore physiologic changes that have greatest influence on TXA disposition. We will test accuracy of PBPK model in isolated hemorrhage and polytrauma swine models and determine if existing dosing guidelines are optimal.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 18, 2018
- Source ID
- HU0001151TS07
Entities
People
- Michael Loughren
Organizations
- Geneva Foundation
- Uniformed Services University of the Health Sciences