To determine the absolute bioavailability of extravascularly administered dexmedetomidine, a novel a2-adrenoceptor agonist, in healthy subjects. Single 2 microg x kg-1 doses of dexmedetomidine were given intravenously, intramuscularly, perorally and buccally (where the solution is not swallowed) to 12 healthy male subjects. The drug concentration-time data were analysed using linear one-compartment (buccal and peroral data), or two-compartment modelling (intravenous data), or noncompartmental methods (intramuscular data). Mean (95% CI) absolute bioavailability after peroral, buccal and intramuscular administration was 16% (12-20%), 82% (73-92%) and 104% (96-112%), respectively. Dexmedetomidine is well absorbed systemically through the oral mucosa, and therefore buccal dosing may provide an effective, noninvasive route to administer the drug.
