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The Effects of Intramuscular Naloxone Dose on Mu Receptor Displacement of Carfentanil in Rhesus Monkeys. | LitMetric

AI Article Synopsis

  • * A new formulation called ZIMHI has been tested, providing a 5 mg IM dose of NLX, but there is limited understanding of its effectiveness via IM administration for mu receptor occupancy (RO).
  • * In a study with rhesus macaques, higher doses of IM NLX were linked to greater mu RO; the findings indicate that higher IM doses could be more effective in treating overdoses from potent synthetic opioids due to a strong correlation between drug levels

Article Abstract

Naloxone (NLX) is a mu receptor antagonist used to treat acute opioid overdoses. Currently approved doses of naloxone to treat opioid overdoses are 4 mg intranasal (IN) and 2 mg intramuscular (IM). However, higher mu receptor occupancy (RO) may be required to treat overdoses due to more potent synthetic opioids such as fentanyl and carfentanil that have entered the illicit drug market recently. To address this need, a higher dose of NLX has been investigated in a 5 mg IM formulation called ZIMHI but, while the effects of intravenous (IV) and IN administration of NLX on the opioid mu receptor occupancy (RO) have been studied, comparatively little is known about RO for IM administration of NLX. The goal of this study was to examine the effect of IM dosing of NLX on mu RO in rhesus macaques using [C]carfentanil positron emission tomography (PET) imaging. The lowest dose of NLX (0.06 mg/kg) approximated 51% RO. Higher doses of NLX (0.14 mg/kg, 0.28 mg/kg) resulted in higher mu RO of 70% and 75%, respectively. Plasma levels were 4.6 ng/mL, 16.8 ng/mL, and 43.4 ng/mL for the three IM doses, and a significant correlation between percent RO and plasma NLX level was observed (r = 0.80). These results suggest that higher doses of IM NLX result in higher mu RO and could be useful in combating overdoses resulting from potent synthetic opioids.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144122PMC
http://dx.doi.org/10.3390/molecules25061360DOI Listing

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