Therapeutic Plasma Concentrations of Epsilon Aminocaproic Acid and Tranexamic Acid in Horses

Journal of Veterinary Internal Medicine

D.J. Fletcher²  B.M. Brainard³  K. Epstein¹  R. Radcliffe² 

[1] the Department of Large Animal Medicine (Epstein), University of Georgia College of Veterinary Medicine, Athens, GA;Department of Clinical Sciences, Cornell University College of Veterinary Medicine, Ithaca, NY;Department of Small Animal Medicine and Surgery, University of Georgia College of Veterinary Medicine, Athens, GA

关键词: Antifibrinolytics;    Bleeding disorders;    Coagulation;    Fibrinolysis;   

DOI  :  10.1111/jvim.12202

来源: Wiley

【 摘 要 】

Abstract

Background

Antifibrinolytic drugs such as epsilon aminocaproic acid (EACA) and tranexamic acid (TEA) are used to treat various bleeding disorders in horses. Although horses are hypofibrinolytic compared to humans, dosing schemes have been derived from pharmacokinetic studies targeting plasma concentrations in humans.

Hypothesis/Objectives

We hypothesized therapeutic plasma concentrations of antifibrinolytic drugs in horses would be significantly lower than in humans. Our objective was to use thromboleastography (TEG) and an in vitro model of hyperfibrinolysis to predict therapeutic concentrations of EACA and TEA in horses and humans.

Animals

Citrated plasma collected from 24 random source clinically healthy research horses. Commercial pooled human citrated plasma with normal coagulation parameters was purchased.

Methods

Minimum tissue plasminogen activator (tPA) concentration to induce complete fibrinolysis within 10 minutes was determined using serial dilutions of tPA in equine plasma. Results used to create an in vitro hyperfibrinolysis model with equine and human citrated plasma, and the minimum concentrations of EACA and TEA required to completely inhibit fibrinolysis for 30 minutes (estimated therapeutic concentrations) determined using serial dilutions of the drugs.

Results

Estimated therapeutic concentrations of EACA and TEA were significantly lower in horses (5.82; 95% CI 3.77–7.86 μg/mL and 0.512; 95% CI 0.277–0.748 μg/mL) than in humans (113.2; 95% CI 95.8–130.6 μg/mL and 11.4; 95% CI 8.62–14.1 μg/mL).

Conclusions and Clinical Importance

Current dosing schemes for EACA and TEA in horses may be as much as 20×  higher than necessary, potentially increasing cost of treatment and risk of adverse effects.

【 授权许可】

Unknown   
Copyright © 2013 by the American College of Veterinary Internal Medicine