Research Article

Bioabsorbable, subcutaneous naltrexone implants mitigate fentanyl‐induced respiratory depression at 3 months—A pilot study in male canines

Published: 2024-8

Journal: Physiological Reports

DOI: 10.14814/phy2.16176

Abstract

The aim of this study is to determine if extended‐release, bioabsorbable, subcutaneous naltrexone (NTX) implants can mitigate respiratory depression after an intravenous injection (IV) of fentanyl. Six different BIOabsorbable Polymeric Implant Naltrexone (BIOPIN) formulations, comprising combinations of Poly‐d,l‐Lactic Acid (PDLLA) and/or Polycaprolactone (PCL‐1 or PCL‐2), were used to create subcutaneous implants. Both placebo and naltrexone implants were implanted subcutaneously in male dogs. The active naltrexone implants consisted of two doses, 644 mg and 1288 mg. A challenge with IV fentanyl was performed in 33 male dogs at 97–100 days after implantation. Following the administration of a 30 μg/kg intravenous fentanyl dose, the placebo cohort manifested a swift and profound respiratory depression with a ~50% reduction in their pre‐dose respiratory rate (RR). The BIOPIN NTX‐implanted dogs were exposed to escalating doses of intravenous fentanyl (30 μg/kg, 60 μg/kg, 90 μg/kg, and 120 μg/kg). In contrast, the dogs implanted with the BIOPIN naltrexone implants tolerated doses up to 60 μg/kg without significant respiratory depression (<50%) but had severe respiratory depression with fentanyl doses of 90 μg/kg and especially at 120 μg/kg. Bioabsorbable, extended‐release BIOPIN naltrexone implants are effective in mitigating fentanyl‐induced respiratory depression in male canines at about 3 months after implantation. This technology may also have potential for mitigating fentanyl‐induced respiratory depression in humans.

Faculty Members

  • Robert L. Joyner - Richard A. Henson Research Institute, TidalHealth Peninsula Regional Salisbury Salisbury Maryland USA
  • Veera Holdai - The Department of Mathematical Sciences Salisbury University Salisbury Maryland USA
  • Steven M. Cohen - The Drug Delivery Company LLC Dba Akyso Salisbury Maryland USA
  • Joseph A. Hollenbaugh - Labcorp Greenfield Indiana USA
  • Donald D'Aquila - Richard A. Henson Research Institute, TidalHealth Peninsula Regional Salisbury Salisbury Maryland USA
  • Marc Fishman - The Department of Psychiatry Johns Hopkins School of Medicine and Maryland Treatment Centers Baltimore Maryland USA
  • Jeffrey D. Benner - Richard A. Henson Research Institute, TidalHealth Peninsula Regional Salisbury Salisbury Maryland USAThe Drug Delivery Company LLC Dba Akyso Salisbury Maryland USA

Themes

  • Veterinary pharmacology
  • Fentanyl administration effects
  • Bioabsorbable polymeric implants
  • Respiratory depression mitigation
  • Effectiveness of naltrexone implants

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