title: Pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid in horses.
abstract: OBJECTIVE
  To determine the pharmacokinetics and pharmacodynamics of epsilon-aminocaproic acid (EACA), including the effects of EACA on coagulation and fibrinolysis in healthy horses.
  
  
  METHODS
  6 adult horses.
  
  
  METHODS
  Each horse received 3.5 mg of EACA/kg/min for 20 minutes, i.v. Plasma EACA concentration was measured before (time 0), during, and after infusion. Coagulation variables and plasma alpha(2)-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 microg/mL; after the end of the infusion, EACA concentration remained greater than the proposed therapeutic concentration (130 microg/mL) for 1 hour. Compared with findings at 0 minutes, EACA administration resulted in no significant change in plasma alpha(2)-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
  Results suggest that EACA has potential clinical use in horses for which improved clot maintenance is desired.
authors.affiliation: Department of Clinical Studies, New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Ross
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Dallap
authors.forename: Brett A
authors.initials: BA
authors.lastname: Dolente
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Sweeney
mesh_terms: D015119:Aminocaproic Acid / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D000933:Antifibrinolytic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006207:Half-Life; D006736:Horses / Q000097:blood / Q000378:metabolism*; D007262:Infusions, Intravenous; D010314:Partial Thromboplastin Time / Q000662:veterinary; D011517:Prothrombin Time / Q000662:veterinary; D018709:Statistics, Nonparametric; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D000933:Antifibrinolytic Agents; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D015119:Aminocaproic Acid