Dexmedetomidine is a novel alpha 2-adrenoceptor agonist that may provide beneficial effects as premedication for anesthesia. The pharmacokinetics and pharmacodynamics of transdermal (TD) and intravenous (i.v.) dexmedetomidine were studied in nine healthy male subjects in a crossover trial. The TD preparation, containing 625 micrograms of dexmedetomidine base, was applied on the forehead and left in place for 12 h. The i.v. dose (2.0 micrograms.kg-1 as dexmedetomidine hydrochloride) was administered as an infusion over 5 min. Dose-normalized total AUC values were used to calculate dexmedetomidine bioavailability. The bioavailability of dexmedetomidine from the TD preparation was 51%. However, the bioavailability of dexmedetomidine released from the preparation was 88%. The mean terminal half-life was 3.1 h after i.v. and 5.6 h after TD administration. After TD administration, the mean maximal reductions in blood pressure (systolic/diastolic) and heart rate were 28/20 mmHg, and 19 beats.min-1. A sedative effect was obvious within 5 min and 1-2 h after i.v. and TD administration, respectively.