Effect of medetomidine on the pharmacokinetics of propofol in dogs

Pharmacokinetic variables of propofol were investigated in 6 mixed-breed dogs, and the effect of medetomidine (10 micrograms/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 micrograms/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 micrograms/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 micrograms/ml) and was 160 minutes in the premedicated dogs in which median blood propofol concentration was 1.03 microgram/ml.