title: PHARMACOKINETIC STUDY OF ORAL ε-AMINOCAPROIC ACID IN THE NORTHERN ELEPHANT SEAL (MIROUNGA ANGUSTIROSTRIS).
abstract: ε-Aminocaproic acid (EACA) is a lysine analogue antifibrinolytic drug used to treat bleeding disorders in humans and domestic animals. Its use in zoological medicine is rare, and dosage is anecdotal. One possible application of EACA is to treat bleeding associated with prepatent Otostrongylus arteritis in Northern elephant seals ( Mirounga angustirostris ) presenting to wildlife rehabilitation centers. This study used an in vitro model of hyperfibrinolysis and a thromboelastograph-based assay to estimate the therapeutic plasma concentration of EACA in elephant seals (85 μg/ml, 95% confidence interval = 73.8-96.8 μg/ml). A concurrent pharmacokinetic study of orally administered, single-dose EACA found that doses of 75 and 100 mg/kg achieved therapeutic plasma concentrations (>85 μg/ml), but the drug was rapidly eliminated and remained in the therapeutic range for only 0.4 and 1.5 hr, respectively. Models of repeated oral dosing at 100 mg/kg every 6 hr predict that therapeutic plasma concentration will be maintained for 31.7% (7.6 hr) of a 24-hr period. More frequent dosing would be required to maintain continuous therapeutic concentrations but would be impractical in a wildlife rehabilitation setting. Further pharmacodynamic studies to evaluate the duration of action of EACA in elephant seals and a prospective, placebo-controlled study are needed to determine if EACA is effective in decreasing bleeding associated with prepatent Otostrongylus arteritis and other bleeding disorders in this species.
authors.forename: Sarrah
authors.initials: S
authors.lastname: Kaye
authors.forename: Shawn
authors.initials: S
authors.lastname: Johnson
authors.forename: Robert D
authors.initials: RD
authors.lastname: Arnold
authors.forename: Ben
authors.initials: B
authors.lastname: Nie
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Davis
authors.forename: Frances
authors.initials: F
authors.lastname: Gulland
authors.forename: Noha
authors.initials: N
authors.lastname: Abou-Madi
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fletcher
mesh_terms: D000284:Administration, Oral; D015119:Aminocaproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000933:Antifibrinolytic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D046048:Seals, Earless / Q000097:blood*
chemical_list: D000933:Antifibrinolytic Agents; D015119:Aminocaproic Acid
keywords: Coagulopathy; Mirounga angustirostris; Northern elephant seal; Otostrongylus circumlitus; thromboelastography; ε-aminocaproic acid