OBJECTIVE: To determine pharmacokinetic variables and to evaluate the influence on clotting times after SC administration of single doses of dalteparin and enoxaparin to horses. ANIMALS: 5 healthy adult horses. PROCEDURES: The study was designed as a 4-period crossover study. Each horse received a single SC injection of dalteparin (50 and 100 anti-Xa U/kg) and enoxaparin (40 and 80 anti-Xa U/kg). Plasma anti-Xa activities and clotting times were measured, and pharmacokinetic variables were determined. Absolute and relative maximal prolongation of clotting times was calculated, and correlation between plasma anti-Xa activities and clotting times was determined. RESULTS: The SC administration of each of the doses of the 2 preparations was well tolerated. Time course of the anti-Xa activities could be described in a 1-compartment model. Comparison of low- and high-dose treatments revealed a disproportionate increase of the area under the plasma activity-time curve and prolongation of the terminal half-life, but the increase in maximum plasma activity was proportionate, and peak plasma concentrations corresponded with concentrations recommended in human medicine. There were only mild changes in activated partial thromboplastin time (aPTT), whereas the influence on thrombin time (TT) was greater, dose-dependent, and more variable. A weak-to-moderate correlation between aPTT and plasma anti-Xa activities and a moderate-to-strong correlation between TT and plasma anti-Xa activities were found. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetic and anticoagulatory properties of low-molecular-weight heparins in horses are similar to those found in humans. Once-daily SC administration of dalteparin or enoxaparin may be useful as an anticoagulatory treatment in horses.
OBJECTIVE: To determine pharmacokinetic variables and to evaluate the influence on clotting times after SC administration of single doses of dalteparin and enoxaparin to horses. ANIMALS: 5 healthy adult horses. PROCEDURES: The study was designed as a 4-period crossover study. Each horse received a single SC injection of dalteparin (50 and 100 anti-Xa U/kg) and enoxaparin (40 and 80 anti-Xa U/kg). Plasma anti-Xa activities and clotting times were measured, and pharmacokinetic variables were determined. Absolute and relative maximal prolongation of clotting times was calculated, and correlation between plasma anti-Xa activities and clotting times was determined. RESULTS: The SC administration of each of the doses of the 2 preparations was well tolerated. Time course of the anti-Xa activities could be described in a 1-compartment model. Comparison of low- and high-dose treatments revealed a disproportionate increase of the area under the plasma activity-time curve and prolongation of the terminal half-life, but the increase in maximum plasma activity was proportionate, and peak plasma concentrations corresponded with concentrations recommended in human medicine. There were only mild changes in activated partial thromboplastin time (aPTT), whereas the influence on thrombin time (TT) was greater, dose-dependent, and more variable. A weak-to-moderate correlation between aPTT and plasma anti-Xa activities and a moderate-to-strong correlation between TT and plasma anti-Xa activities were found. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetic and anticoagulatory properties of low-molecular-weight heparins in horses are similar to those found in humans. Once-daily SC administration of dalteparin or enoxaparin may be useful as an anticoagulatory treatment in horses.
Authors: Andrea Corda; Nicolò Columbano; Valentina Secchi; Antonio Scanu; Maria Luisa Pinna Parpaglia; Giovanni Mario Careddu; Eraldo Sanna Passino Journal: Open Vet J Date: 2020-09-15