The pharmacokinetics of propofol in laboratory animals

1. The pharmacokinetics of propofol in an emulsion formulation ('Diprivan') have been studied after single bolus doses to rats, dogs, rabbits and pigs, and after single and multiple infusions to dogs. Venous blood propofol concentrations were determined by h.p.l.c. with u.v. or fluorescence detection. Curve fitting was performed using ELSFIT. 2. The distribution of propofol in blood and its plasma protein binding have been studied in rat, dog, rabbit and man. Protein binding was high (96-98%), and in most species propofol showed appreciable association with the formed elements of blood. 3. Where an adequate sampling period was employed the pharmacokinetics of propofol were best described by a three-compartment open 'mammillary' model. Propofol was distributed into a large initial volume (1-21/kg) and extensively redistributed (Vss = 2-10 x body weight) in all species. Clearance of propofol by all species was rapid, ranging from about 30-80 ml/kg per min in rats, dogs and pigs to about 340 ml/kg per min in rabbits.