title: Clinical signs, laboratory changes and toxicokinetics of brodifacoum in the horse.
abstract: Six horses gavaged with a commercial brodifacoum (BDF)-containing bait (Talone) at a dosage of 0.125 mg of BDF/kg of body weight showed weight loss, severe hypocoagulability and hemogram alterations. Four of the horses became depressed and anorectic; one required vitamin K1 therapy. Increases in clotting times were observed at 24 h in the partial thromboplastin time (PTT) followed by the thrombotest (TBT) and one-stage prothrombin time (PT) at 48 h. Elevated mean PTT, PT and TBT were observed from days 4 to 8 (p less than 0.05) with levels returning to pretreatment levels by day 12. Maximum prolongation was a fourfold increase in PTT (day 4), a 2.5-fold increase in TBT (day 6) and a twofold increase in PT (day 6). Thrombin clotting times remained unchanged. In two horses prolongation in clotting time did not normalize until day 23. The mean hematocrit (0.38 +/- 0.01 L/L) was decreased (p less than 0.05) from day 8 (0.33 +/- 0.02 L/L) to day 14 (0.33 +/- 0.01 L/L). The hemoglobin concentration and erythrocyte numbers were decreased (p less than 0.05) from day 6 (20.1%, 17.6% respectively) to day 14 (22%, 20% respectively). Platelet counts decreased on day 6 (17.2%) to nine (14.6%). No other significant changes were observed in routine hematological and serum biochemical parameters. Peak plasma concentrations of BDF occurred 2 to 3 h after oral administration; two horses had detectable levels of BDF at nine days. Pharmacokinetic evaluation indicated that BDF has a half-life of 1.22 +/- 0.22 days, a body clearance of 1073.1 +/- 53.21 mL/kg/day, a volume of distribution of 1853.7 +/- 26.41 ng-day/mL and closely approximates a one-compartment model in the elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph.
authors.forename: H J
authors.initials: HJ
authors.lastname: Boermans
authors.forename: I
authors.initials: I
authors.lastname: Johnstone
authors.forename: W D
authors.initials: WD
authors.lastname: Black
authors.forename: M
authors.initials: M
authors.lastname: Murphy
mesh_terms: D015110:4-Hydroxycoumarins / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000662:veterinary; D001777:Blood Coagulation / Q000187:drug effects; D004906:Erythrocyte Count / Q000187:drug effects / Q000662:veterinary; D005260:Female; D006400:Hematocrit / Q000662:veterinary; D006454:Hemoglobins / Q000032:analysis / Q000187:drug effects; D006734:Horse Diseases / Q000139:chemically induced*; D006736:Horses; D008297:Male; D010976:Platelet Count / Q000187:drug effects / Q000662:veterinary; D012378:Rodenticides / Q000493:pharmacokinetics / Q000633:toxicity*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D015110:4-Hydroxycoumarins; D006454:Hemoglobins; D012378:Rodenticides; C013418:bromfenacoum