Clinical Pharmacokinetic Analysis and Modeling of Tranexamic Acid in Dogs

Abstract

Tranexamic Acid (TXA) is an FDA approved drug for hemophilia patients undergoing dental extractions and women experiencing heavy bleeding during menstrual periods. It is also used to stop bleeding and decrease risk of hyperfibrinolysis during surgeries and in patients with injuries. TXA competitively binds to plasminogen at the lysine residue’s site preventing its activation to plasmin. This inhibits fibrinolysis and maintains clots for longer times. Hyperfibrinolysis is an abnormal increase in the rate of clot degradation that increases the risk of acute coagulopathy of trauma and shock. This acute condition is induced by a hemostatic imbalance leading to increased blood loss and increased mortality. We determined TXA pharmacokinetics in dogs following single dose administration in 6 healthy mix-breed dogs receiving 10 mg/Kg 10 minutes IV infusion, 20 mg/Kg 10 minutes IV infusion, 15 mg/Kg PO, and 20 mg/Kg PO in a randomized cross-over design using non-compartmental and computational methods to examine different dosing schedules. The overall goal of this research project was to assist investigators in designing further clinical studies to establish the TXA exposure-response relationships and optimize the clinical the effect of different dosing regimens.