title: Pharmacokinetics of dexmedetomidine infusions for sedation of postoperative patients requiring intensive caret.
abstract: BACKGROUND
  The pharmacokinetics of the alpha-2 adrenoceptor agonist dexmedetomidine were studied in 10 patients requiring postoperative sedation and mechanical ventilation in the intensive care unit (ICU), and compared with previous volunteer data.
  
  
  METHODS
  On arrival in the ICU, sedation with dexmedetomidine was commenced with a loading dose of 2.5 microg kg(-1) h(-1) over 10 min followed by a maintenance infusion of 0.7 microg kg(-1) h(-1) into a central vein. Blood samples for measurement of plasma dexmedetomidine concentrations were taken during and after sedative infusions at predetermined intervals. Pharmacokinetic variables were estimated using non-compartmental methods. In addition, non-linear mixed effects modelling was used to obtain variable estimates not readily attainable from non-compartmental methods. Respiratory and haemodynamic data were recorded to enable correlation of any adverse events with the calculated pharmacokinetic profile.
  
  
  RESULTS
  The harmonic mean distribution half-life of dexmedetomidine was 8.6 min and the harmonic mean terminal half-life was 3.14 h. Steady-state volume of distribution averaged 173 litres, clearance averaged 48.3 litres h(-1), and the mean residence time averaged 3.86 h.
  
  
  CONCLUSIONS
  Mean dexmedetomidine pharmacokinetic variables seen in postoperative, intensive care patients were similar to those previously found in volunteers, with the exception of the steady-state volume of distribution. A small loading dose provided effective sedation with no adverse events.
authors.affiliation: Department of Anaesthesia and Intensive Care, Worthing Hospital, West Sussex, UK.
authors.forename: R M
authors.initials: RM
authors.lastname: Venn
authors.forename: M D
authors.initials: MD
authors.lastname: Karol
authors.forename: R M
authors.initials: RM
authors.lastname: Grounds
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000097:blood* / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016292:Procedural Sedation / Q000379:methods; D003422:Critical Care / Q000379:methods*; D020927:Dexmedetomidine / Q000097:blood* / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011182:Postoperative Care / Q000379:methods*; D012119:Respiration / Q000187:drug effects; D012121:Respiration, Artificial
chemical_list: D000316:Adrenergic alpha-Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine