Pharmacokinetic study of oral amitriptyline in horses |
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Authors: | Lucciana Recchi Silvana Alvariza Alejandro Benech Natalie Ruiz María José Estradé Gonzalo Suarez Nadia Crosignani |
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Institution: | 1. Department of Veterinary Pharmacology, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay;2. Department of Small Animal Medicine, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay;3. Department of Animal Reproduction, Faculty of Veterinary Medicine, Universidad de la República, Montevideo, Uruguay |
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Abstract: | The purpose of this study was to evaluate the pharmacokinetics of oral amitriptyline in horses. Oral amitriptyline (1 mg/kg) was administered to six horses. Blood samples were collected from jugular and lateral thoracic vein at predetermined times from 0 to 24 hr after administration. Plasma concentrations were determined by high-performance liquid chromatography and analyzed using noncompartmental methods. Pharmacodynamic parameters including heart rate, respiration rate, and intestinal motility were evaluated, and electrocardiographic examinations were performed in all subjects. The mean maximum plasma concentration (Cmax) of amitriptyline was 30.7 ng/ml, time to maximum plasma concentration (Tmax) 1–2 hr, elimination half-life (t1/2) 17.2 hr, area under plasma concentration–time curve (AUC) 487.4 ng ml?1 hr?1, apparent clearance (Cl/F) 2.6 L hr?1 kg?1, and apparent volume of distribution (Vd/F) 60.1 L/kg. Jugular vein sampling overestimated the amount of amitriptyline absorbed and should not be used to study uptake following oral administration. Heart rate and intestinal motility showed significant variation (p < .05). Electrocardiography did not provide conclusive results. Further studies are required to discern if multiple dose treatment would take the drug to steady state as expected, consequently increasing plasma concentrations. |
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Keywords: | analgesia antidepressive agents chronic pain pharmacology |
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