An Ultra-Long-Acting Buprenorphine Prodrug Ion-Pair for Opioid Use Disorder

Abstract

Opioid overdose is a significant global public health concern. While buprenorphine (BUP) is a safe and effective treatment for opioid use disorder (OUD), requirements for frequent dosing and patient tolerability to organic solvent based monthly injectables limit its use. These challenges were overcome by the development of a scalable ultra-long-acting (ULA) BUP (NM6BUP-Pamoate). The binding of a lipophilic BUP prodrug to a hydrophobic counterion generated an organic-solvent-free formulation. A single dose of NM6BUP-Pamoate administered to Sprague–Dawley rats at 45 mg/kg produced sustained effective plasma BUP levels for six months. Brain BUP concentrations exceeded the recorded plasma levels. Safety evaluations demonstrated the absence of off-target toxicities, with local and systemic tolerability. NM6BUP-Pamoate simplifies OUD treatment to optimize clinical outcomes.

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Cite

BibTeX RIS

BibTeX

@misc{edagwa2026ultralongacting,
  title = {{An Ultra-Long-Acting Buprenorphine Prodrug Ion-Pair for Opioid Use Disorder}},
  author = {Benson Edagwa and Ashrafi Sultana and Nam Thai Hoang Le and Mohammad Ullah Nayan and Brady Sillman and Sunday Ogundepo and Chen Zhang and Brandon Hanson and Suyash Deodhar and Xiaoqing Du and Samuel Cohen and Brian Kearney and Alborz Yazdi and Howard Gendelman},
  howpublished = {Research Square},
  year = {2026},
  month = nov,
  doi = {10.21203/rs.3.rs-11194855/v1},
  url = {https://doi.org/10.21203/rs.3.rs-11194855/v1},
  note = {CC BY 4.0},
}

RIS

TY  - UNPB
TI  - An Ultra-Long-Acting Buprenorphine Prodrug Ion-Pair for Opioid Use Disorder
AU  - Benson Edagwa
AU  - Ashrafi Sultana
AU  - Nam Thai Hoang Le
AU  - Mohammad Ullah Nayan
AU  - Brady Sillman
AU  - Sunday Ogundepo
AU  - Chen Zhang
AU  - Brandon Hanson
AU  - Suyash Deodhar
AU  - Xiaoqing Du
AU  - Samuel Cohen
AU  - Brian Kearney
AU  - Alborz Yazdi
AU  - Howard Gendelman
PY  - 2026
DA  - 2026/11/01
PB  - Research Square
DO  - 10.21203/rs.3.rs-11194855/v1
UR  - https://doi.org/10.21203/rs.3.rs-11194855/v1
AB  - Opioid overdose is a significant global public health concern. While buprenorphine (BUP) is a safe and effective treatment for opioid use disorder (OUD), requirements for frequent dosing and patient tolerability to organic solvent based monthly injectables limit its use. These challenges were overcome by the development of a scalable ultra-long-acting (ULA) BUP (NM6BUP-Pamoate). The binding of a lipophilic BUP prodrug to a hydrophobic counterion generated an organic-solvent-free formulation. A single dose of NM6BUP-Pamoate administered to Sprague–Dawley rats at 45 mg/kg produced sustained effective plasma BUP levels for six months. Brain BUP concentrations exceeded the recorded plasma levels. Safety evaluations demonstrated the absence of off-target toxicities, with local and systemic tolerability. NM6BUP-Pamoate simplifies OUD treatment to optimize clinical outcomes.
SN  - 2693-5015
ER  -

Abstract

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