Development of a nalmefene formulation suitable for a community-use auto-injector.
Alessandra Cipriano, Manjunath S Shet, Hugh Huang et al.
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In 30 seconds
This preclinical and clinical formulation study evaluated whether magnesium chloride could accelerate intramuscular nalmefene absorption and reversal of opioid-induced respiratory depression. After screening absorption enhancers in animals, investigators assessed formulations in healthy participants, including a randomized six-period crossover study in six participants with fentanyl-induced respiratory depression. Nalmefene 1.5 mg with 0.94% magnesium chloride was absorbed more rapidly than a formulation with 0.9% sodium chloride and produced faster, more robust reversal than intranasal naloxone. The findings support further consideration of this formulation for community-use auto-injectors, but the clinical evidence comes from a small healthy-participant study.
Key findings
- In animal studies, magnesium chloride across a range of concentrations enhanced nalmefene absorption.
- Nalmefene 1.5 mg with 0.94% magnesium chloride was absorbed more rapidly than nalmefene formulated with 0.9% sodium chloride.
- In six participants with fentanyl-induced respiratory depression, the magnesium chloride formulation produced faster, more robust reversal than intranasal naloxone.
Why it matters
Rapid reversal is important in opioid-induced respiratory depression, particularly where immediate life support is unavailable. These findings suggest that formulation can influence intramuscular nalmefene absorption and reversal speed, and provide translational evidence relevant to developing a community-use auto-injector. They do not establish effectiveness in people experiencing opioid overdose outside the controlled study setting.
What to keep in mind
The clinical evaluation was small and conducted in healthy participants with experimentally induced respiratory depression, rather than in people experiencing opioid overdose.