Metabolism,pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses |
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| Institution: | 1. K.L. Maddy Equine Analytical Pharmacology Laboratory, University of California-Davis, School of Veterinary Medicine, Davis, CA, USA;2. Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, USA;3. Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA;1. Department of Animal Medicine Production and Health, University of Padova, Padova, Italy;2. Department of Animal Sciences, Stellenbosch University, Stellenbosch, South Africa;3. Wildlife Pharmaceuticals (Pty) Ltd., White River, South Africa;4. School of Veterinary and Life Sciences, Murdoch University, Perth, Australia;5. Wildlifevets.com, Ngongoni Game Lodge, Karino, South Africa;6. Centre for Nutrition and Food Sciences, Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, Brisbane, Australia;1. Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA;2. Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA;1. Clinic for Ruminants with Ambulatory and Herd Health Services, Ludwig-Maximilians-University Munich, Germany;2. Center of Preclinical Research, Klinikum rechts der Isar, Technical University Munich, Germany;3. German Center for Neurodegenerative Diseases, Munich, Germany;1. Boston Children''s Hospital, Boston, Massachusetts, USA;2. Harvard Medical School, Boston, Massachusetts, USA;3. Northeastern University, Boston, Massachusetts, USA |
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| Abstract: | ObjectiveTo describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration.Study designProspective experimental study.AnimalsA total of 12 Thoroughbred horses, nine geldings and three mares, aged 4–8 years.MethodsHorses were administered codeine (0.6 mg kg–1) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography–mass spectrometry, and plasma pharmacokinetics were determined. Heart rate and rhythm, step counts, packed cell volume and total plasma protein were measured before and 4 hours after administration.ResultsCodeine was rapidly converted to the metabolites norcodeine, codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Plasma codeine concentrations were best represented using a two-compartment model. The Cmax, tmax and elimination t½ were 270.7 ± 136.0 ng mL–1, 0.438 ± 0.156 hours and 2.00 ± 0.534 hours, respectively. M3G was the main metabolite detected (Cmax 492.7 ± 35.5 ng mL–1), followed by C6G (Cmax 96.1 ± 33.8 ng mL–1) and M6G (Cmax 22.3 ± 4.96 ng mL–1). Morphine and norcodeine were the least abundant metabolites with Cmax of 3.17 ± 0.95 and 1.42 ± 0.79 ng mL–1, respectively. No significant adverse or excitatory effects were observed.Conclusions and clinical relevanceFollowing oral administration, codeine is rapidly metabolized to morphine, M3G, M6G, C6G and norcodeine in horses. Plasma concentrations of M6G, a presumed active metabolite of morphine, were comparable to concentrations reported previously following administration of an analgesic dose of morphine to horses. Codeine was well tolerated based on pharmacodynamic variables and behavioral observations. |
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| Keywords: | codeine horse metabolism pharmacodynamics pharmacokinetics |
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