WHAT IS KNOWN AND 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. WHAT IS NEW AND CONCLUSION: 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.