title: Validation of fentanyl pharmacokinetics in patients undergoing coronary artery bypass grafting.
abstract: OBJECTIVE
  The current emphasis on more rapid recovery and earlier tracheal extubation after cardiac surgery requires greater precision in administering opioids to reap their benefits while minimizing the duration of postoperative respiratory depression. Therefore, we aimed to define a pharmacokinetic model that accurately predicts fentanyl concentrations before, during, and after cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting (CABG).
  
  
  METHODS
  Parameters for two-compartment and three-compartment models were estimated by applying population pharmacokinetic modelling to fentanyl concentration vs time data measured in 29 patients undergoing elective, primary CABG. The ability of these models to predict fentanyl concentrations in a second series of ten patients undergoing CABG was then assessed.
  
  
  RESULTS
  A simple, three-compartment model had excellent predictive ability, with a median prediction error (PE = ([Fentanyl]meas - [Fentanyl]pred)/[Fentanyl]pred x 100%) of -0.5%, and a median absolute PE (APE = /PE/) of 14.0%. In comparison to the two-compartment models, linear regression of measured:predicted concentration ratios indicated that the three-compartment model was free of systematic and time-related changes in bias (P < 0.05). The parameters of this three-compartment model are: V1 15.0 l, V2 20.0 l, V3 86.1 l, Cl1 1.08 L x min(-1), Cl2 4.90 L x min(-1), and Cl3 2.60 L x min(-1).
  
  
  CONCLUSIONS
  Our pharmacokinetic model provides a rational foundation for designing fentanyl dose regimens for patients undergoing CABG. When combined with previously published information regarding intraoperative fentanyl pharmacodynamics, dose regimens that reliably achieve and maintain desired fentanyl concentrations throughout the intraoperative period can be designed to achieve specific therapeutic goals.
authors.affiliation: Department of Anesthesia, University of Manitoba, St. Boniface General Hospital, Winnipeg, Manitoba, Canada. rhudson@cc.manitoba.ca
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hudson
authors.forename: Ian R
authors.initials: IR
authors.lastname: Thomson
authors.forename: Blair T
authors.initials: BT
authors.lastname: Henderson
authors.forename: Karanbir
authors.initials: K
authors.lastname: Singh
authors.forename: Gary
authors.initials: G
authors.lastname: Harding
authors.forename: David J
authors.initials: DJ
authors.lastname: Peterson
mesh_terms: D000368:Aged; D000465:Algorithms; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D000758:Anesthesia; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D005260:Female; D005283:Fentanyl / Q000097:blood / Q000493:pharmacokinetics*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D011446:Prospective Studies
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl