title: Pharmacokinetics of a new, nasal formulation of naloxone.
abstract: OBJECTIVE
  Nasal naloxone is wanted for bystander administration in opioid overdose and as a needle-free alternative for emergency medical personnel. Epidemiologic studies have indicated a therapeutic effect of bystander administration of low-concentration/high-volume formulations. The objective for this study was to describe the nasal pharmacokinetics of a new high-concentration/low-volume nasal formulation of naloxone.
  
  
  METHODS
  This was an open, randomized triple crossover trial in healthy, human volunteers (n = 12) where two doses of nasal naloxone (0.8 and 1.6 mg) and one intravenous dose (1.0 mg) were compared. Fifteen serum samples were collected before and until 6 h after naloxone administration. Quantification of naloxone was performed by a validated liquid chromatography-tandem mass spectrometry method.
  
  
  RESULTS
  Bioavailability was 0.54 (0.45-0.63) for the 0.8 mg and 0.52 (0.37-0.67) for the 1.6 mg nasal naloxone formulation. Maximum concentration levels (Cmax) were 1.45 ng/ml (1.07-1.84) for 0.8 mg and 2.57 ng/ml (1.49-3.66) for the 1.6 mg. Time to maximum concentrations (Tmax) were reached at 17.9 min (11.4-24.5) and 18.6 min (14.4-22.9) for the 0.8 mg and the 1.6 mg doses, respectively.
  
  
  CONCLUSIONS
  This nasal naloxone formulation had a rapid, systemic uptake and higher bioavailability than naloxone formulations not designed for IN use. This indicates that an optimized high-concentration/low-volume nasal spray formulation may deliver a therapeutic dose. The 1.6 mg nasal dose provided serum concentrations that surpassed those of 1.0 mg IV after 15-20 min and stayed above for the rest of the study period.
authors.affiliation: Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ida
authors.initials: I
authors.lastname: Tylleskar
authors.affiliation: Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.|Division of Emergencies and Critical Care, Department of Anaesthesiology, Oslo University Hospital, Oslo, Norway.
authors.forename: Arne Kristian
authors.initials: AK
authors.lastname: Skulberg
authors.affiliation: Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Turid
authors.initials: T
authors.lastname: Nilsen
authors.affiliation: Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Sissel
authors.initials: S
authors.lastname: Skarra
authors.affiliation: Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Phatsawee
authors.initials: P
authors.lastname: Jansook
authors.affiliation: Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. ola.dale@ntnu.no.|Department of Research and Development, St. Olav's University Hospital, Trondheim, Norway. ola.dale@ntnu.no.
authors.forename: Ola
authors.initials: O
authors.lastname: Dale
mesh_terms: D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone
keywords: Bioavailability; Intranasal; Naloxone; Nasal; Overdose; Pharmacokinetics