Bioavailability of dexmedetomidine after extravascular doses in healthy subjects

Abstract

Aim To determine the absolute bioavailability of extravascularly administered dexmedetomidine, a novel a2-adrenoceptor agonist, in healthy subjects. Methods Single 2 m g 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). Results Mean (95% CI) absolute bioavailability after peroral, buccal and intramuscular administration was 16% (12-20%), 82% (73-92%) and 104% (96-112%), respectively. Conclusion Dexmedetomidine is well absorbed systemically through the oral mucosa, and therefore buccal dosing may provide an effective, noninvasive route to administer the drug.

Dexmedetomidine in Current Anaesthesia Practice- A Review

“…However, after sublingual & intranasal administration bioavailability is high (84%), giving it a potential role in paediatric sedation and premedication [8].…”

Dosing and efficacy of intranasal dexmedetomidine sedation for pediatric transthoracic echocardiography: a retrospective study

“…11 Indeed, in one study, buccal dosing resulted in a peak dexmedetomidine serum concentration in 90 min, while intranasal dosing gave a peak serum level at 38 min. 10,12 Nevertheless, the appropriate dose of intranasal dexmedetomidine to facilitate sedation for TTE is not known. Moreover, the hemodynamic side effects of dexmedetomidine, which could be dose-dependent and especially prevalent in children with congenital heart disease, have not been adequately explored in this patient population.…”

“…It also seems devoid of the local discomfort frequently associated with intranasal administration of midazolam, rendering it very attractive for brief sedation during echocardiography. [6][7][8][9] The bioavailability of orally administered dexmedetomidine is very poor at 16% (12-20%) with a peak at two hours 10 ; however, the intranasal route has shown to be more effective than the buccal (i.e., sublingual) route of administration when using equal doses of dexmedetomidine premedication in children. 11 Indeed, in one study, buccal dosing resulted in a peak dexmedetomidine serum concentration in 90 min, while intranasal dosing gave a peak serum level at 38 min.…”

Dexmedetomidina: papel atual em anestesia e cuidados intensivos

“…An interesting future for dexmedetomidine is oral or nasal dexmedetomidine administration for pediatric sedation as oral absorption of dexmedetomidine is 82% when compared with intravenous administration 62 . Nasal dexmedetomidine administration has also been shown to be a well tolerated and effective route for sedation in adults 63 , and has also been shown to be comparable with oral midazolam to decrease preoperative agitation 64 .…”