Document Detail


Propofol alters the pharmacokinetics of alfentanil in healthy male volunteers.
MedLine Citation:
PMID:  11465619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M J Mertens; J Vuyk; E Olofsen; J G Bovill; A G Burm
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anesthesiology     Volume:  94     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-07-23     Completed Date:  2001-08-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  949-57     Citation Subset:  AIM; IM    
Affiliation:
Department of Anesthesiology, Leiden University Medical Center, The Netherlands. m.j.mertens@lumc.nl
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MeSH Terms
Descriptor/Qualifier:
Adult
Alfentanil / pharmacokinetics*
Algorithms
Analgesics, Opioid / pharmacokinetics*
Anesthetics, Intravenous / pharmacology*
Computer Simulation
Drug Interactions
Hemodynamics / drug effects
Humans
Male
Models, Biological
Propofol / pharmacology*
Chemical
Reg. No./Substance:
0/Analgesics, Opioid; 0/Anesthetics, Intravenous; 2078-54-8/Propofol; 71195-58-9/Alfentanil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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