Disposition kinetics of propofol during alfentanil anaesthesia

The pharmacokinetics of a constant rate infusion of propofol were studied in 11 patients who received total intravenous anaesthesia for ENT surgery. Alfentanil was administered as an exponentially decreasing infusion using a computer-assisted infusion device with a constant target plasma alfentanil concentration of 300 ng/ml. Propofol was infused at a constant rate of 6 mg/kg/hours. Plasma alfentanil concentrations were determined by gas chromatography and whole blood propofol concentrations by high-performance liquid chromatography in arterial blood samples collected at selected times during and up to 8 hours after infusion. Pharmacokinetic modelling of the blood propofol concentration-time data indicated that a three-compartment open model with central elimination was most appropriate. Derived pharmacokinetic parameters were in agreement with previous studies on the pharmacokinetics of propofol. The plasma alfentanil concentrations in 10 patients significantly exceeded the expected values at any time during the infusion. The population mean bias amounted to 20.2% (SD 12.6). Only three data sets were significantly underestimated after the infusion was stopped (mean bias 11.9% (SD 25.5]. The elimination half-life of alfentanil was approximately 75 minutes (SD 21). We conclude that alfentanil does not interfere with the pharmacokinetic profile of propofol but that propofol induces higher plasma alfentanil concentrations than expected.