Pharmacokinetics of S-ketamine and R-ketamine and their active metabolites after racemic ketamine or S-ketamine intravenous administration in dogs sedated with medetomidine |
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| Institution: | 1. Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy;2. Anaesthesiology Section, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland;3. Epidemiology Section, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland;1. Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA;2. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI, USA;1. Anesthesiology and Pain Management, Department of Comparative, Diagnostic, and Population Medicine, College of Veterinary Medicine, University of Florida, 2015 SW 16th Av, P.O. Box 1000123, Gainesville, FL 32610-0123, USA;2. Department of Anesthesiology and Pain Management, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, Argentina;1. Willows Veterinary Centre & Referral Service, Shirley, Solihull, UK;2. Department of Applied Physics/Electro-Optics, Jerusalem College of Technology, Yerushalayim, Israel;1. Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA;2. Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA;3. Department of Biological and Diagnostic Services, College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA;4. Office of Information and Technology, University of Tennessee, Knoxville, TN, USA;5. Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, CA, USA |
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| Abstract: | ObjectiveTo assess the differences in the pharmacokinetic profiles of S-ketamine, R-ketamine and their metabolites, S-norketamine and R-norketamine, and to measure relevant physiologic variables after intravenous administration of racemic (RS) ketamine or S-ketamine alone in Beagle dogs sedated with medetomidine.Study designExperimental, blinded and randomized crossover study.AnimalsA total of six (three female and three male) adult Beagle dogs.MethodsMedetomidine (450 μg m–2) was administered intramuscularly, followed by either S-ketamine (2 mg kg–1) or RS-ketamine (4 mg kg–1) 20 minutes later, both administered intravenously. Blood samples were collected before medetomidine administration and at multiple time points 1–900 minutes following the ketamine administration. Plasma samples were analysed using liquid chromatography–tandem mass spectrometry. Heart rate, respiratory rate, noninvasive blood pressure, haemoglobin saturation with oxygen and body temperature were measured at baseline, before ketamine administration, and 1, 2, 5, 10, 15, 20 and 30 minutes after ketamine administration. All cardiovascular variables, blood glucose, haemoglobin and lactate concentrations were analysed using different linear mixed effects models; the significance was set at p < 0.05.ResultsS-ketamine showed a two-compartment kinetic profile; no statistically significant differences were observed between its concentrations or in the calculated pharmacokinetic parameters following S- or RS-ketamine. When the racemic mixture was administered, no differences were detected between R- and S-ketamine concentrations, but the area under the curve (AUC) for R-norketamine was significantly lower than that for S-norketamine. Clinically relevant physiologic variables did not show statistically significant differences following the administration of the racemic mixture or of S-ketamine alone.Conclusions and clinical relevanceThis study performed in dogs showed that RS-ketamine and S-ketamine combined with medetomidine showed enantioselective pharmacokinetics as S- and R-norketamine AUCs were different, but S-ketamine levels were identical. |
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| Keywords: | canine medetomidine pharmacokinetics S-ketamine S-norketamine |
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