Dose-dependent plasma elimination of subcutaneously administered calcium heparin in horses

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Abstract
Pharmacokinetic parameters for subcutanewous low dose heparin in horses have been determined. Four groups of five and one group of eleven mature, healthy horses of various breeds were given single subcutaneous injections of 60, 80, 100, 125, and 150 units of calcium heparin/kg of body weight (U/kg) in the pectoral region. Jugular blood samples were collected prior to, and at hourly intervals for 12 h after injection. Heparin plasma concentrations were measured using a commercially available amidolytic assay. Peak concentrations 4 h after administration were 0.021 .+-. 0.016 (mean .+-. SD) units of heparin/ml of plasma (U/ml) after 60 U/kg, 0.034 .+-. 0.025 U/ml afer 80 U/kg, 0.023 .+-. 0.004 U/ml after 100 U/kg, 0.034 .+-. 0.019 U/ml after 125 U/kg, and 0.053 .+-. 0.019 U/ml after 150 U/kg. Data from groups given 60 and 100 U/kg could not be used for kinetic calculations. Elimination constnat (1/h), elimination half-life, and elimination time (h) calculated to reach base-line values after 80 U/kg were 0.182 .+-. 0.041 1/h, 3.8 .+-. 0.9 h, and 9.7 .+-. 2.2 h. After 125 U/kg, corresponding values were 0.211 .+-. .+-. 0.019 1/h, 3.3 .+-. 0.3 h, 13.4 .+-. 1.2 h, and after 150 U/kg 0.098 .+-. 0.015 1/h, 7.1 .+-. 1.1 h, and 20.6 .+-. 3.2 h. Calculated heparin concentrations 12 h after administration of 80, 125, and 150 U/kg were 0.011 .+-. 0.002, 0.010 .+-. 0.001, and 0.027 .+-. 0.004 U/ml. After seven successive injections of 150 U/kg at 12 h intervals in one horse, the elimination constant decreased from 0.23/h after the first to 0.08/h after the seventh injection, and the elimination time increased from 10 to 40 h. Reducing the dosage from 150 U/kg initially to 125 U/kg from six successive injections reduced the prolonged elimination after repeated injections.