Effect of medetomidine on the pharmacokinetics of propofol in dogs

Leslie W. Hall From the Department of Veterinary Clinical Medicine, University of Cambridge, Cambridge, CB3 7BQ England (Hall), Department of Veterinary Anesthesia, University of Utrecht, Utrecht, The Netherlands (Lagerweij), Department of Veterinary Pharmacology, University of Glasgow, Glasgow, G61 1QH Scotland (Nolan), and Department of Anesthesia, University of Oxford, Oxford, 0X3 9DU England (Sear).

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Evert Lagerweij From the Department of Veterinary Clinical Medicine, University of Cambridge, Cambridge, CB3 7BQ England (Hall), Department of Veterinary Anesthesia, University of Utrecht, Utrecht, The Netherlands (Lagerweij), Department of Veterinary Pharmacology, University of Glasgow, Glasgow, G61 1QH Scotland (Nolan), and Department of Anesthesia, University of Oxford, Oxford, 0X3 9DU England (Sear).

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Andrea M. Nolan From the Department of Veterinary Clinical Medicine, University of Cambridge, Cambridge, CB3 7BQ England (Hall), Department of Veterinary Anesthesia, University of Utrecht, Utrecht, The Netherlands (Lagerweij), Department of Veterinary Pharmacology, University of Glasgow, Glasgow, G61 1QH Scotland (Nolan), and Department of Anesthesia, University of Oxford, Oxford, 0X3 9DU England (Sear).

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John W. Sear From the Department of Veterinary Clinical Medicine, University of Cambridge, Cambridge, CB3 7BQ England (Hall), Department of Veterinary Anesthesia, University of Utrecht, Utrecht, The Netherlands (Lagerweij), Department of Veterinary Pharmacology, University of Glasgow, Glasgow, G61 1QH Scotland (Nolan), and Department of Anesthesia, University of Oxford, Oxford, 0X3 9DU England (Sear).

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Summary

Pharmacokinetic variables of propofol were investigated in 6 mixed-breed dogs, and the effect of medetomidine (10 μg/kg of body weight) on these kinetics was investigated using a two-way crossover design. On 2 occasions, dogs received either a bolus dose of propofol sufficient to allow endotracheal intubation, followed by an infusion of propofol (0.4 mg/kg/min) for 120 minutes, or medetomidine (10 μg/kg, im), 15 minutes prior to induction of anesthesia as described, followed by infusion of propofol (0.2 mg/kg/min). Dogs given medetomidine received atipamezole (50 μg/kg, im) at the end of the 120-minute propofol infusion. Blood propofol concentration was measured, using high-performance liquid chromatography with fluorescence detection. Mean elimination half-life, blood clearance, mean residence time, and mean volume of distribution at steady state, were 486.2 minutes, 34.4 ml/kg/min, 301.8 minutes, and 6.04 L/kg, respectively, in the absence of medetomidine, and 136.9 minutes, 36.2 ml/ kg/min, 215.1 minutes, and 3.38 L/kg, respectively, in the presence of medetomidine. Mean time to walking without ataxia was 174 minutes in the nonpremedicated dogs (with a median blood propofol concentration of 2.2 μg/ml) and was 160 minutes in the premedicated dogs in which median blood propofol concentration was 1.03 μg/ml.

Summary

Pharmacokinetic variables of propofol were investigated in 6 mixed-breed dogs, and the effect of medetomidine (10 μg/kg of body weight) on these kinetics was investigated using a two-way crossover design. On 2 occasions, dogs received either a bolus dose of propofol sufficient to allow endotracheal intubation, followed by an infusion of propofol (0.4 mg/kg/min) for 120 minutes, or medetomidine (10 μg/kg, im), 15 minutes prior to induction of anesthesia as described, followed by infusion of propofol (0.2 mg/kg/min). Dogs given medetomidine received atipamezole (50 μg/kg, im) at the end of the 120-minute propofol infusion. Blood propofol concentration was measured, using high-performance liquid chromatography with fluorescence detection. Mean elimination half-life, blood clearance, mean residence time, and mean volume of distribution at steady state, were 486.2 minutes, 34.4 ml/kg/min, 301.8 minutes, and 6.04 L/kg, respectively, in the absence of medetomidine, and 136.9 minutes, 36.2 ml/ kg/min, 215.1 minutes, and 3.38 L/kg, respectively, in the presence of medetomidine. Mean time to walking without ataxia was 174 minutes in the nonpremedicated dogs (with a median blood propofol concentration of 2.2 μg/ml) and was 160 minutes in the premedicated dogs in which median blood propofol concentration was 1.03 μg/ml.

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