Abstract
Objective—To determine the pharmacokinetics and pharmacodynamics of ϵ-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses.
Animals—6 adult horses.
Procedures—Each horse received 3.5 mg of EACA/kg/min for 20 minutes, IV. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma α2-antiplasmin activity were evaluated at time 0 and 4 hours after infusion; viscoelastic properties of clot formation were assessed at time 0 and 0.5, 1, and 4 hours after infusion. Plasma concentration versus time data were evaluated by use of a pharmacokinetic analysis computer program.
Results—Drug disposition was best described by a 2-compartment model with a rapid distribution phase, an elimination half-life of 2.3 hours, and mean residence time of 2.5 ± 0.5 hours. Peak plasma EACA concentration was 462.9 ± 70.1 μg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 μg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma α2-antiplasmin activity at 1 or 4 hours after infusion. Thirty minutes after infusion, platelet function was significantly different from that at time 0 and 1 and 4 hours after infusion. The continuous rate infusion that would maintain proposed therapeutic plasma concentrations of EACA was predicted (ie, 3.5 mg/kg/min for 15 minutes, then 0.25 mg/kg/min).
Conclusions and Clinical Relevance—Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.
