Kt. Kivisto et al., PHARMACOKINETICS AND PHARMACODYNAMICS OF TRANSDERMAL DEXMEDETOMIDINE, European Journal of Clinical Pharmacology, 46(4), 1994, pp. 345-349
Dexmedetomidine is a novel alpha(2)-adrenoceptor agonist that may prov
ide beneficial effects as premedication for anesthesia. The pharmacoki
netics and pharmacodynamics of transdermal (TD) and intravenous (IV) d
exmedetomidine were studied in nine healthy male subjects in a crossov
er trial. The TD preparation, containing 625 mu g of dexmedetomidine b
ase, was applied on the forehead and left in place for 12 h. The IV do
se (2.0 mu g.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 bioavail
ability of dexmedetomidine released from the preparation was 88%. The
mean terminal half-life was 3.1 h after IV and 5.6 h after TD administ
ration. After TD administration, the mean maximal reductions in blood
pressure (systolic/diastolic) and heart rate were 28/20 mmHg and 19 be
ats.min(-1). A sedative effect was obvious within 5 min and 1-2 h afte
r IV and TD administration, respectively.