title: Pharmacokinetics of dexmedetomidine in Chinese post-surgical intensive care unit patients.
abstract: BACKGROUND
  Dexmedetomidine is a rather new drug in China. We sought to describe the pharmacokinetics of dexmedetomidine in patients requiring post-operative sedation and ventilation in our surgical intensive care unit.
  
  
  METHODS
  Twenty-two patients received post-operative infusions of dexmedetomidine at 6 μg/kg/h for 10 min, followed by 0.4 μg/kg/h for 350 min. Venous blood samples were drawn and assayed for plasma concentration. The pharmacokinetics were analysed using a nonlinear mixed-effect model with an interindividual and intraindividual error model. An initial estimation was performed to determine which of the one-, two- or three-compartment models is best to describe the concentration-time data. The covariates age, gender, weight, height, lean body mass (LBM), body surface area (BSA) and body mass index (BMI) were tested for significant effects on parameters using a stepwise forward addition and backward elimination approach. Covariate effects were judged based on changes in the objective function value (OFV).
  
  
  RESULTS
  The pharmacokinetics of dexmedetomidine were best described by a three-compartment model. The model was further improved when height was a covariate of systemic clearance (Cl1), with a decrease in OFV by -13.56 (P<0.01). From the heights of 155-178 cm, Cl1 increased by approximately 143%. The final pharmacokinetic parameter values were as follows: V1 =63.4 l, V2=41.3 l, V3 =284.3 l, Cl1=0.47×(height/160 cm)(6.42) l/min, Cl2=2.43 l/min and Cl3=0.086 l/min.
  
  
  CONCLUSIONS
  This study identified (i) the effect of height on the pharmacokinetics of dexmedetomidine; (ii) that there is no influence of age, gender, weight, LBM, BSA and BMI on pharmacokinetic parameters; and (iii) it established a preliminary population pharmacokinetic model for Chinese patients.
authors.affiliation: Pediatric Clinical Pharmacology Laboratory, Department of Anesthesiology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, and Department of Anesthesiology and Surgical Intensive Care Unit, Shanghai Yangpu District Hospital, Shanghai, China.
authors.forename: L
authors.initials: L
authors.lastname: Lin
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.forename: M-Z
authors.initials: MZ
authors.lastname: Zhang
authors.forename: C-J
authors.initials: CJ
authors.lastname: Qu
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: J
authors.initials: J
authors.lastname: Bai
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000494:pharmacology; D020927:Dexmedetomidine / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000700:Analgesics; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine