title: End-stage renal failure reduces central clearance and prolongs the elimination half life of remifentanil.
abstract: OBJECTIVE
  To evaluate the pharmacokinetics of remifentanil in 13 end-stage renal failure patients compared to matched control patients with normal renal function.
  
  
  METHODS
  Remifentanil was infused for 20 min at a rate of 0.1 microg x kg(-1) x min(-1). Serial arterial blood samples (3 mL) were drawn at the start of infusion (zero), five, ten, 15, 20, 22.5, 25, 27.5, 30, 35, 40, 45, 50, 55 and 60 min. Blood samples were immediately preserved with citric acid and chilled on ice. High performance liquid chromatography-tandem mass spectrometry concentration assay was performed using GI 95779B internal standard.
  
  
  RESULTS
  A two-compartment pharmacokinetic model provided an adequate fit for individual patient data. There was no difference in the mean +/- SD distribution half life (t1/2) between the renal failure group (1.65 +/- 0.7 min) and the control group (1.58 +/- 0.54 min). There was a significant difference in the central clearance (Cl(c)) and elimination half life (t1/2) ss) between the renal failure group (28 +/- 7 mL x kg(-1) x min(-1) and 18.86 +/- 2.06 min, respectively) and the control group (46.3 +/- 13.8 mL x kg(-1) x min(-1) and 16.35 +/- 2.99 min, respectively). Remifentanil blood concentrations were significantly higher in the renal failure group than in the control group.
  
  
  CONCLUSIONS
  We have demonstrated a significant reduction in the Cl(c) and a prolongation of t1/2 ss of remifentanil in end-stage renal failure patients. While statistically significant, these variations in the pharmacokinetics of remifentanil were clinically modest and may be explained by a reduced volume of distribution in the period following hemodialysis.
authors.affiliation: Departments of Anaesthesiology and Intensive Care Medicine, and Medical Chemistry and Pregl Laboratory, Karl-Franzens University, Graz, Austria. Ashraf.Dahaba@kfunigraz.ac.at
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Dahaba
authors.forename: Karl
authors.initials: K
authors.lastname: Oettl
authors.forename: Fedor
authors.initials: F
authors.lastname: von Klobucar
authors.forename: Gilbert
authors.initials: G
authors.lastname: Reibnegger
authors.forename: Werner F
authors.initials: WF
authors.lastname: List
mesh_terms: D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D017711:Nonlinear Dynamics; D010880:Piperidines / Q000493:pharmacokinetics*; D011446:Prospective Studies; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil