Pharmacokinetics of propofol administered by infusion in dogs undergoing surgery

We have investigated the pharmacokinetics of propofol in seven beagle dogs undergoing surgery for implantation of s.c. tissue pouches. Blood concentrations of propofol were measured using high pressure liquid chromatography with fluorescence detection. After premedication with acepromazine and papaveretum and induction of anaesthesia with propofol 4 mg kg-1 i.v., anaesthesia was maintained with propofol 0.4 mg kg-1 min-1 and 67% nitrous oxide in six dogs. In the seventh dog, the infusion rate was increased to 0.6 mg kg-1 min-1 in order to achieve surgical anaesthesia. The mean elimination half-life was 322.3 (sem 27.0) min, mean volume of distribution at steady state 6.510 (0.524) litre kg-1, mean body clearance 50.1 (3.9) ml kg-1 min-1 and mean residence time 131.6 (8.9) min. The blood propofol concentrations achieved using this standard dosing regimen showed wide variation among individuals. All dogs recovered rapidly from anaesthesia. The mean time to extubation was 7.6 min and to standing unaided was 30.7 min from the end of the infusion.