title: Remifentanil pharmacokinetics in obese versus lean patients.
abstract: BACKGROUND
  Remifentanil is a short-acting opioid whose pharmacokinetics have been characterized in detail. However, the impact of obesity on remifentanil pharmacokinetics has not been specifically examined. The goal of this study was to investigate the influence of body weight on remifentanil pharmacokinetics.
  
  
  METHODS
  Twelve obese and 12 matched lean subjects undergoing elective surgery received a 1-min remifentanil infusion after induction of anesthesia. Arterial blood samples were collected for determination of remifentanil blood concentrations. Each subject's pharmacokinetic parameters were estimated by fitting a two-compartment model to the concentration versus time curves. Nonlinear mixed-effects population models examining the influence of lean body mass (LBM) and total body weight (TBW) were also constructed. Clinical simulations using the final population model were performed.
  
  
  RESULTS
  The obese patient cohort reached substantially higher remifentanil concentrations. The individual pharmacokinetic parameters of a two-compartment model were not significantly different between the obese versus lean cohorts (unless normalized to TBW). The final population model scaled central clearance and the central and peripheral distribution volumes to LBM. The simulations illustrated that remifentanil pharmacokinetics are not grossly different in obese versus lean subjects and that TBW based dosing in obese patients can result in excessively high remifentanil concentrations.
  
  
  CONCLUSIONS
  The essential findings of the study are that remifentanil's pharmacokinetics are not appreciably different in obese versus lean subjects and that remifentanil pharmacokinetic parameters are therefore more closely related to LBM than to TBW. Clinically this means that remifentanil dosing regimens should be based on ideal body weight (or LBM) and not TBW.
authors.affiliation: Department of Anesthesiology, University of Utah Health Sciences Center in Salt Lake City, 84132, USA. TEGAN@anesth.med.utah.edu
authors.forename: T D
authors.initials: TD
authors.lastname: Egan
authors.forename: B
authors.initials: B
authors.lastname: Huizinga
authors.forename: S K
authors.initials: SK
authors.lastname: Gupta
authors.forename: R L
authors.initials: RL
authors.lastname: Jaarsma
authors.forename: R J
authors.initials: RJ
authors.lastname: Sperry
authors.forename: J B
authors.initials: JB
authors.lastname: Yee
authors.forename: K T
authors.initials: KT
authors.lastname: Muir
mesh_terms: D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D001835:Body Weight; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010880:Piperidines / Q000493:pharmacokinetics*; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil