Propofol alters the pharmacokinetics of alfentanil in healthy male volunteers

Background: The influence of propofol on the pharmacokinetics of alfentanil is poorly understood. The authors therefore studied the effect of a pseudo -study state concentration of propofol on the pharmacokinetics of alfentani l. Methods: The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week inter val. While breathing 30% O-2 in air, 12.5 mug/kg intravenous alfentanil was given in 2 min, followed by 25 mug . kg(-1) h(-1) for 58 min (sessions A a nd B). During session B, a target controlled infusion of propofol (target c oncentration, 1.5 mug/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac outpu t, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal ca rbon dioxide were monitored. Venous blood samples for determination of the plasma alfentanil concentration were collected until 6 h after termination of the alfentanil infusion. Nonlinear mixed-effects population pharmacokine tic models examining the influence of propofol and mean arterial pressure w ere constructed. Results: A three-compartment model, including a lag time accounting for the venous blood sampling, adequately described the concentration-time curves of alfentanil. Propofol decreased the elimination clearance of alfentanil b y 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resi stance were significantly lower in the presence of propofol. Scaling the ph armacokinetic parameters to the mean arterial pressure instead of propofol improved the model. Conclusions: Propofol alters the pharmacokinetics of alfentanil. Hemodynami c changes induced by propofol may have an important influence on the pharma cokinetics of alfentanil.