OBJECTIVE Dexmedetomidine is a selective alpha2-adrenoreceptor agonist used for sedation in critically ill patients. The current study aimed to evaluate the pharmacokinetics (PKs), pharmacodynamics and tolerability of intravenous dexmedetomidine in healthy Korean subjects. METHODS A randomized, double-blind, placebo-controlled study with three parallel dosage groups was conducted. Twenty-four subjects were randomly assigned to placebo or one of three dexmedetomidine dosing regimens, 3 μg/kg/h for 10 min followed by 0.17 μg/kg/h for 50 min (low dose), 6 μg/kg/h for 10 min followed by 0.34 μg/kg/h for 50 min (middle dose) and 3.7 μg/kg/h for 35 min followed by 0.7 μg/kg/h for 25 min (high dose). Serial blood samples for PK analysis were taken up to 12 h. PK parameters were determined using non-compartmental methods (WinNonlin(®)), and a population PK model was developed using nonmem(®). The sedative effect of dexmedetomidine was assessed by Ramsay sedation score and visual analogue scales/sedation. Adverse events, clinical laboratory tests, electrocardiograms, physical examinations and vital signs were monitored for tolerability assessment. RESULTS Six subjects were assigned to each of the three active treatment group or placebo group. The AUC(last) of the low-, middle- and high-dose group were 1096.8 ± 119.9 (mean ± SD) ng*h/L, 2643.0 ± 353.2 ng*h/L and 5600.6 ± 411.0 ng*h/L, respectively. PK of dexmedetomidine was best described using a two-compartment model. The typical value of the population model can be calculated using the following equations: central volume of distribution (L) = 19.9 (age/27)(0.954), peripheral volume of distribution (L) = 59.4, clearance (L/h) = 33.7 (albumin level/4.3)(1.42) and inter-compartment clearance (L/h) = 67.7. Sedative effects were significantly increased by dexmedetomidine compared to placebo. The blood pressure and heart rate were decreased, but oxygen saturation was maintained stable. CONCLUSIONS Dexmedetomidine shows linear PK characteristics and dose-dependent sedative effects. A two-compartment population PK model was developed for healthy Korean subjects. The PK parameter estimates are similar in Koreans and Caucasians.