title: The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers.
abstract: BACKGROUND
  Remifentanil (GI87084B) is a new short-acting opioid with a unique ester structure. Metabolism of remifentanil by ester hydrolysis results in very rapid elimination. The aim of this study was to characterize in detail the pharmacokinetic profile of remifentanil in healthy male volunteers.
  
  
  METHODS
  Ten healthy adult male volunteers received a zero-order infusion of remifentanil at doses ranging from 1 to 8 micrograms.kg-1.min-1 for 20 min. Frequent arterial blood samples were drawn and analyzed by gas chromatographic mass spectroscopy to determine the remifentanil blood concentrations. The raw pharmacokinetic data were analyzed using three different parametric compartmental modeling methods (traditional two-stage, naive pooled data, and NONMEM). The raw pharmacokinetic data also were analyzed using numeric deconvolution and a nonparametric moment technique. A computer simulation using hte pharmacokinetic parameters of the NONMEM compartmental model was performed to provide a more intuitively meaningful and clinically relevant description of the pharmacokinetics. The simulation estimated the time necessary to achieve a 50% decrease in remifentanil concentration after a variable-length infusion.
  
  
  RESULTS
  For each parametric method, a three-compartment mamillary model that accurately describes remifentanil's concentration decay curve was constructed. The NONMEM analysis population pharmacokinetic parameters included a central clearance of 2.8 l/min, a volume of distribution at steady state of 32.8 l, and a terminal half-life of 48 min. The mean results of the nonparametric moment analysis included a clearance of 2.9 l/min, a volume of distribution at steady state of 31.8 l, and a mean residence time of 10.9 min. The computer simulation revealed the strikingly unique pharmacokinetic profile of remifentanil compared to that of the currently available fentanyl family of opioids.
  
  
  CONCLUSIONS
  Remifentanil is a new, short-acting opioid with promising clinical potential in anesthesiology.
authors.affiliation: Department of Anesthesiology, University of Utah School of Medicine, Salt Lake City 84132.
authors.forename: T D
authors.initials: TD
authors.lastname: Egan
authors.forename: H J
authors.initials: HJ
authors.lastname: Lemmens
authors.forename: P
authors.initials: P
authors.lastname: Fiset
authors.forename: D J
authors.initials: DJ
authors.lastname: Hermann
authors.forename: K T
authors.initials: KT
authors.lastname: Muir
authors.forename: D R
authors.initials: DR
authors.lastname: Stanski
authors.forename: S L
authors.initials: SL
authors.lastname: Shafer
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D000077208:Remifentanil
chemical_list: D000701:Analgesics, Opioid; D010880:Piperidines; D000077208:Remifentanil