title: Population pharmacokinetics of dexmedetomidine during long-term sedation in intensive care patients.
abstract: BACKGROUND
  Dexmedetomidine is a highly selective and potent α(2)-adrenoceptor agonist registered for sedation of patients in intensive care units. There is little information on factors possibly affecting its pharmacokinetics during long drug infusions in critically ill patients. We characterized the pharmacokinetics of dexmedetomidine in critically ill patients during long-term sedation using a population pharmacokinetic approach.
  
  
  METHODS
  Twenty-one intensive care patients requiring sedation and mechanical ventilation received dexmedetomidine with a loading dose of 3-6 µg kg(-1) h(-1) in 10 min and a maintenance dose of 0.1-2.5 µg kg(-1) h(-1) for a median duration of 96 h (range, 20-571 h). Cardiac output (CO), laboratory and respiratory parameters, and dexmedetomidine concentrations in arterial plasma were measured. The pharmacokinetics was determined by population analysis using linear multicompartment models.
  
  
  RESULTS
  The pharmacokinetics of dexmedetomidine was best described by a two-compartment model. The population values (95% confidence interval) for elimination clearance, inter-compartmental clearance, central volume of distribution, and volume of distribution at steady state were 57.0 (42.1, 65.6), 183 (157, 212) litre h(-1), 12.3 (7.6, 17.0), and 132 (96, 189) litre. Dexmedetomidine clearance decreased with decreasing CO and with increasing age, whereas its volume of distribution at steady state was increased in patients with low plasma albumin concentration.
  
  
  CONCLUSIONS
  The population pharmacokinetics of dexmedetomidine was generally in line with results from previous studies. In elderly patients and in patients with hypoalbuminaemia, the elimination half-life and the context-sensitive half-time of dexmedetomidine were prolonged.
authors.affiliation: Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, Turku, Finland. tiirola@utu.fi
authors.forename: T
authors.initials: T
authors.lastname: Iirola
authors.forename: H
authors.initials: H
authors.lastname: Ihmsen
authors.forename: R
authors.initials: R
authors.lastname: Laitio
authors.forename: E
authors.initials: E
authors.lastname: Kentala
authors.forename: R
authors.initials: R
authors.lastname: Aantaa
authors.forename: J-P
authors.initials: JP
authors.lastname: Kurvinen
authors.forename: M
authors.initials: M
authors.lastname: Scheinin
authors.forename: H
authors.initials: H
authors.lastname: Schwilden
authors.forename: J
authors.initials: J
authors.lastname: Schüttler
authors.forename: K T
authors.initials: KT
authors.lastname: Olkkola
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood; D016292:Procedural Sedation / Q000379:methods*; D003422:Critical Care / Q000379:methods*; D020927:Dexmedetomidine / Q000008:administration & dosage / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D012121:Respiration, Artificial; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine