title: Bioavailability of dexmedetomidine after intranasal administration.
abstract: OBJECTIVE
  The aim of this proof-of-concept study was to characterize the pharmacokinetics and pharmacodynamics of intranasal dexmedetomidine compared with its intravenous administration in a small number of healthy volunteers.
  
  
  METHODS
  Single doses of 84 μg of dexmedetomidine were given once intravenously and once intranasally to seven healthy men. Plasma dexmedetomidine concentrations were measured for 10 h, and pharmacokinetic variables were calculated with standard noncompartmental methods. Heart rate, blood pressure, concentrations of adrenaline and noradrenaline in plasma, and central nervous system drug effects (with the Maddox wing, Bispectral Index, and three visual analog scales) were monitored to assess the pharmacological effects of dexmedetomidine.
  
  
  RESULTS
  Six individuals were included in the analyses. Following intranasal administration, peak plasma concentrations of dexmedetomidine were reached in 38 (15-60) min and its absolute bioavailability was 65% (35-93%) (medians and ranges). Pharmacological effects were similar with both routes of administration, but their onset was more rapid after intravenous administration.
  
  
  CONCLUSIONS
  Dexmedetomidine is rather rapidly and efficiently absorbed after intranasal administration. Compared with intravenous administration, intranasal administration may be a feasible alternative in patients requiring light sedation.
authors.affiliation: Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, P.O. Box 52, FI-20521, Turku, Finland. tiirola@utu.fi
authors.forename: Timo
authors.initials: T
authors.lastname: Iirola
authors.forename: Sanna
authors.initials: S
authors.lastname: Vilo
authors.forename: Tuula
authors.initials: T
authors.lastname: Manner
authors.forename: Riku
authors.initials: R
authors.lastname: Aantaa
authors.forename: Maria
authors.initials: M
authors.lastname: Lahtinen
authors.forename: Mika
authors.initials: M
authors.lastname: Scheinin
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Olkkola
mesh_terms: D000281:Administration, Intranasal; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000328:Adult; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D016292:Procedural Sedation / Q000379:methods*; D003243:Consciousness / Q000187:drug effects; D018592:Cross-Over Studies; D020927:Dexmedetomidine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004837:Epinephrine / Q000097:blood; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009297:Nasal Mucosa / Q000187:drug effects; D009638:Norepinephrine / Q000097:blood; D012894:Sleep Stages / Q000187:drug effects
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D009638:Norepinephrine; D004837:Epinephrine