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-steady state concentration of propofol on the pharmacokinetics of alfentanil.


METHODS
The pharmacokinetics of alfentanil was studied on two occasions in eight male volunteers in a randomized crossover manner with a 3-week interval. While breathing 30% O2 in air, 12.5 microg/kg intravenous alfentanil was given in 2 min, followed by 25 microg.kg(-1).h(-1) for 58 min (sessions A and B). During session B, a target controlled infusion of propofol (target concentration, 1.5 microg/ml) was given from 10 min before the start until 6 h after termination of the alfentanil infusion. Blood pressure, cardiac output, electrocardiogram, respiratory rate, oxygen saturation, and end-tidal carbon 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 pharmacokinetic models examining the influence of propofol and mean arterial pressure were 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 by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%. Mean arterial pressure and systemic vascular resistance were significantly lower in the presence of propofol. Scaling the pharmacokinetic parameters to the mean arterial pressure instead of propofol improved the model.


CONCLUSIONS
Propofol alters the pharmacokinetics of alfentanil. Hemodynamic changes induced by propofol may have an important influence on the pharmacokinetics of alfentanil.
Mertens
M J
MJ
Department of Anesthesiology, Leiden University Medical Center, The Netherlands. m.j.mertens@lumc.nl
Vuyk
J
J
Olofsen
E
E
Bovill
J G
JG
Burm
A G
AG
D000328:Adult; D015760:Alfentanil / Q000493:pharmacokinetics*; D000465:Algorithms; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D003198:Computer Simulation; D004347:Drug Interactions; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008954:Models, Biological; D015742:Propofol / Q000494:pharmacology*
D000701:Analgesics, Opioid; D018686:Anesthetics, Intravenous; D015760:Alfentanil; D015742:Propofol