EFFECT OF MEDETOMIDINE ON THE PHARMACOKINETICS OF PROPOFOL IN DOGS

Pharmacokinetic variables of propofol were investigated in 6 mixed-bre ed dogs, and the effect of medetomidine (10 mug/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 t o allow endotracheal intubation, followed by an infusion of propofol ( 0.4 mg/kg/min) for 120 minutes, or medetomidine (10 mug/kg, im), 15 mi nutes prior to induction of anesthesia as described, followed by infus ion of propofol (0.2 mg/kg/min). Dogs given medetomidine received atip amezole (50 mug/kg, im) at the end of the 120-minute propofol infusion . Blood propofol concentration was measured, using high-performance li quid chromatography with fluorescence detection. Mean elimination half -life, blood clearance, mean residence time, and mean volume of distri bution at steady state, were 486.2 minutes, 34.4 ml/kg/min, 301.8 minu tes, 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, respectiv ely, in the presence of medetomidine. Mean time to walking without ata xia was 174 minutes in the nonpremedicated dogs (with a median blood p ropofol concentration of 2.2 mug/ml) and was 160 minutes in the premed icated dogs in which median blood propofol concentration was 1.03 mug/ ml.