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Eur J Clin Pharmacol. 2017 Jan 31. doi: 10.1007/s00228-016-2191-1. [Epub ahead of print]

Pharmacokinetics of a new, nasal formulation of naloxone.

Author information

  • 1Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
  • 2Division of Emergencies and Critical Care, Department of Anaesthesiology, Oslo University Hospital, Oslo, Norway.
  • 3Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
  • 4Department of Circulation and Medical Imaging, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. ola.dale@ntnu.no.
  • 5Department of Research and Development, St. Olav's University Hospital, Trondheim, Norway. ola.dale@ntnu.no.

Abstract

PURPOSE:

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 (C max) 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 (T max) 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.

CONCLUSION:

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.

KEYWORDS:

Bioavailability; Intranasal; Naloxone; Nasal; Overdose; Pharmacokinetics

PMID:
28144724
DOI:
10.1007/s00228-016-2191-1
[PubMed - as supplied by publisher]
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