Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats

Daphnée Veilleux-Lemieux,1,2 Francis Beaudry,1 Pierre Hélie,3 Pascal Vachon11Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe, 2Department of Veterinary Services, Laval University, Quebec, 3Department of Pathology and Microbiology, Universit...

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Autores principales: Vachon P, Hélie P, Beaudry F, Veilleux-Lemieux D
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:ab86d81dc8a943928a781ccda86e93e52021-12-02T07:52:23ZEffects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats2230-2034https://doaj.org/article/ab86d81dc8a943928a781ccda86e93e52012-10-01T00:00:00Zhttp://www.dovepress.com/effects-of-endotoxemia-on-the-pharmacodynamics-and-pharmacokinetics-of-a11190https://doaj.org/toc/2230-2034Daphnée Veilleux-Lemieux,1,2 Francis Beaudry,1 Pierre Hélie,3 Pascal Vachon11Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe, 2Department of Veterinary Services, Laval University, Quebec, 3Department of Pathology and Microbiology, University of Montreal, Saint-Hyacinthe, CanadaPurpose: To evaluate the effects of endotoxemia on the pharmacokinetics and pharmacodynamics of ketamine and xylazine anesthesia in Sprague–Dawley rats.Methods: Sprague–Dawley rats received ketamine (80 mg/kg) and xylazine (5 mg/kg) intramuscularly following the intraperitoneal administration of different lipopolysaccharide concentrations (1, 10, and 100 µg/kg) to simulate different levels of endotoxemia. Results were compared to control animals receiving saline intraperitoneally. During anesthesia, a toe pinch was performed to evaluate anesthesia duration, and selected physiological parameters (heart and respiratory rates, oxygen saturation, and rectal temperature) were taken. Blood samples were also taken during anesthesia at selected time points for the analysis of plasmatic ketamine and xylazine concentrations by liquid chromatography–mass spectrometry. Blood samples were taken 1 week prior to and 24 hours following anesthesia for blood biochemistry.Results: Anesthesia duration significantly increased for moderate (10 µg/kg) and high (100 µg/kg) lipopolysaccharide groups. Liver histopathology showed minor to moderate necrosis in all lipopolysaccharide groups in some animals. The most important physiological change that occurred was a decrease in oxygen saturation, and for blood biochemistry a decrease in serum albumin. Ketamine pharmacokinetics were not affected except for the moderate (10 µg/kg) lipopolysaccharide group where a decrease in the area under the plasma concentration–time curve from time zero to the last measurable concentration, a decrease in half-life, and an increase in the clearance were observed. For xylazine, the area under the plasma concentration–time curve increased and the clearance decreased in the moderate (10 µg/kg) and high (100 µg/kg) lipopolysaccharide groups.Conclusion: During ketamine–xylazine anesthesia, endotoxemia may alter xylazine pharmacokinetics and selected biochemical and physiological parameters, suggesting that anesthetic drug dosages could be modified for a more rapid recovery.Keywords: lipopolysaccharide, ketamine, xylazine, pharmacokinetics, ratsVachon PHélie PBeaudry FVeilleux-Lemieux DDove Medical PressarticleVeterinary medicineSF600-1100ENVeterinary Medicine: Research and Reports, Vol 2012, Iss default, Pp 99-109 (2012)
institution DOAJ
collection DOAJ
language EN
topic Veterinary medicine
SF600-1100
spellingShingle Veterinary medicine
SF600-1100
Vachon P
Hélie P
Beaudry F
Veilleux-Lemieux D
Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats
description Daphnée Veilleux-Lemieux,1,2 Francis Beaudry,1 Pierre Hélie,3 Pascal Vachon11Department of Veterinary Biomedicine, University of Montreal, Saint-Hyacinthe, 2Department of Veterinary Services, Laval University, Quebec, 3Department of Pathology and Microbiology, University of Montreal, Saint-Hyacinthe, CanadaPurpose: To evaluate the effects of endotoxemia on the pharmacokinetics and pharmacodynamics of ketamine and xylazine anesthesia in Sprague–Dawley rats.Methods: Sprague–Dawley rats received ketamine (80 mg/kg) and xylazine (5 mg/kg) intramuscularly following the intraperitoneal administration of different lipopolysaccharide concentrations (1, 10, and 100 µg/kg) to simulate different levels of endotoxemia. Results were compared to control animals receiving saline intraperitoneally. During anesthesia, a toe pinch was performed to evaluate anesthesia duration, and selected physiological parameters (heart and respiratory rates, oxygen saturation, and rectal temperature) were taken. Blood samples were also taken during anesthesia at selected time points for the analysis of plasmatic ketamine and xylazine concentrations by liquid chromatography–mass spectrometry. Blood samples were taken 1 week prior to and 24 hours following anesthesia for blood biochemistry.Results: Anesthesia duration significantly increased for moderate (10 µg/kg) and high (100 µg/kg) lipopolysaccharide groups. Liver histopathology showed minor to moderate necrosis in all lipopolysaccharide groups in some animals. The most important physiological change that occurred was a decrease in oxygen saturation, and for blood biochemistry a decrease in serum albumin. Ketamine pharmacokinetics were not affected except for the moderate (10 µg/kg) lipopolysaccharide group where a decrease in the area under the plasma concentration–time curve from time zero to the last measurable concentration, a decrease in half-life, and an increase in the clearance were observed. For xylazine, the area under the plasma concentration–time curve increased and the clearance decreased in the moderate (10 µg/kg) and high (100 µg/kg) lipopolysaccharide groups.Conclusion: During ketamine–xylazine anesthesia, endotoxemia may alter xylazine pharmacokinetics and selected biochemical and physiological parameters, suggesting that anesthetic drug dosages could be modified for a more rapid recovery.Keywords: lipopolysaccharide, ketamine, xylazine, pharmacokinetics, rats
format article
author Vachon P
Hélie P
Beaudry F
Veilleux-Lemieux D
author_facet Vachon P
Hélie P
Beaudry F
Veilleux-Lemieux D
author_sort Vachon P
title Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats
title_short Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats
title_full Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats
title_fullStr Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats
title_full_unstemmed Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in Sprague–Dawley rats
title_sort effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine and xylazine anesthesia in sprague–dawley rats
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/ab86d81dc8a943928a781ccda86e93e5
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