Development of a nalmefene formulation suitable for a community-use auto-injector

Area of Science:

• Pharmacology
• Drug Delivery
• Emergency Medicine

Background:

• Opioid-induced respiratory depression (OIRD) requires rapid reversal.
• Nalmefene is an opioid antagonist used to treat OIRD.
• Intramuscular administration aims for faster absorption compared to other routes.

Purpose of the Study:

• To develop an improved nalmefene formulation for faster intramuscular absorption.
• To reduce the time to onset of reversal for OIRD.
• To evaluate the efficacy of the new formulation compared to existing treatments.

Main Methods:

• Screening of absorption enhancers in rats and dogs.
• Clinical studies in healthy participants evaluating nalmefene formulations with varying MgCl2 concentrations.
• Assessment of pharmacokinetics and pharmacodynamics in participants experiencing fentanyl-induced OIRD, comparing MgCl2-nalmefene, intranasal naloxone, and placebo.

Main Results:

• Preclinical studies confirmed MgCl2 enhances nalmefene absorption rate.
• Clinical trials showed a nalmefene formulation with 0.94% MgCl2 achieved faster absorption than a NaCl formulation.
• The MgCl2-nalmefene formulation demonstrated quicker and more effective reversal of OIRD than intranasal naloxone.

Conclusions:

• A nalmefene formulation with magnesium chloride significantly enhances absorption via intramuscular injection.
• This improved formulation offers a faster onset of action for treating OIRD.
• The rapid absorption makes this formulation particularly valuable for emergency treatment of opioid overdose where immediate life support is not accessible.