title: Population pharmacokinetics of dexmedetomidine in critically ill patients.
abstract: OBJECTIVE
  Although the pharmacokinetics of dexmedetomidine in healthy volunteers have been studied, there are limited data about the pharmacokinetics of long-term administration of dexmedetomidine in critically ill patients.
  
  
  METHODS
  This population pharmacokinetic analysis was performed to quantify the pharmacokinetics of dexmedetomidine in critically ill patients following infusions up to 14 days in duration. The data consisted of three phase III studies (527 patients with sparse blood sampling, for a total of 2,144 samples). Covariates were included in a full random-effects covariate model and the most important covariate relationships were tested separately. The linearity of dexmedetomidine clearance was evaluated by observing steady-state plasma concentrations acquired at various infusion rates.
  
  
  RESULTS
  The data were adequately described with a one-compartment model. The clearance of dexmedetomidine was 39 (95 % CI 37-41) L/h and volume of distribution 104 (95 % CI 93-115) L. Both clearance and volume of distribution were highly variable between patients (coefficients of variation of 62 and 57 %, respectively), which highlights the importance of dose titration by response. Covariate analysis showed a strong correlation between body weight and clearance of dexmedetomidine. The clearance of dexmedetomidine was constant in the dose range 0.2-1.4 μg/kg/h.
  
  
  CONCLUSIONS
  The pharmacokinetics of dexmedetomidine are dose-proportional in prolonged infusions when dosing rates of 0.2-1.4 μg/kg/h, recommended by the Dexdor(®) summary of product characteristics, are used.
authors.affiliation: Faculty of Health Sciences, School of Pharmacy, University of Eastern Finland, PO Box 1624, 70211, Kuopio, Finland. pyry.valitalo@uef.fi
authors.forename: Pyry Antti
authors.initials: PA
authors.lastname: Välitalo
authors.forename: Tuula
authors.initials: T
authors.lastname: Ahtola-Sätilä
authors.forename: Andrew
authors.initials: A
authors.lastname: Wighton
authors.forename: Toni
authors.initials: T
authors.lastname: Sarapohja
authors.forename: Pasi
authors.initials: P
authors.lastname: Pohjanjousi
authors.forename: Chris
authors.initials: C
authors.lastname: Garratt
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000493:pharmacokinetics*; D000368:Aged; D016638:Critical Illness; D020927:Dexmedetomidine / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D020927:Dexmedetomidine