Reversal of Fentanyl‐Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene Administered by Auto‐Injector Versus Intranasal Naloxone.
As illegally made fentanyl and congeners continue to drive overdose deaths in the US, experts have called for stronger and longer‐lasting antagonists. A randomized, 4‐period, 2‐treatment crossover replicate‐design study in healthy moderately‐experienced opioid users (n = 24) evaluated the reversal o...
| Publicado en: | Journal of Clinical Pharmacology Vol. 65; no. 12; pp. 1661 - 1676 |
|---|---|
| Autores principales: | , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Dec2025
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=189709628&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 189709628 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Dec2025 vid: 65 iid: 12 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 189709628 187277114 189709628 189709628 10.1002/jcph.70088 189709628 ppf: 1661 ppct: 15 formats: tig: atl: Reversal of Fentanyl‐Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene Administered by Auto‐Injector Versus Intranasal Naloxone. aug: au: Cipriano, Alessandra He, Ellie Shet, Manjunath Apseloff, Glen Harris, Stephen C. affil: Imbrium Therapeutics L.P., a subsidiary of Purdue Pharma L.P., Stamford Connecticut,, USA sug: subj: Fentanyl Adverse Effects Respiration Disorders Drug Therapy Narcotic Antagonists Administration and Dosage Injections, Intramuscular Naloxone Administration and Dosage Administration, Intranasal Drug Delivery Systems Funding Source Human Male Female Adolescence Adult Middle Age Confidence Intervals Descriptive Statistics Fentanyl Administration and Dosage Fentanyl Pharmacokinetics Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: As illegally made fentanyl and congeners continue to drive overdose deaths in the US, experts have called for stronger and longer‐lasting antagonists. A randomized, 4‐period, 2‐treatment crossover replicate‐design study in healthy moderately‐experienced opioid users (n = 24) evaluated the reversal of opioid‐induced respiratory depression (OIRD) by intramuscular (IM) nalmefene 1.5 mg administered by auto‐injector delivering a formulation developed for faster onset, compared to intranasal (IN) naloxone 4 mg. Fentanyl infusions were administered to induce a 50% reduction in minute ventilation (MV). Reversal of OIRD, pharmacokinetics, and safety were investigated under steady‐state fentanyl agonism. For the primary endpoint, nalmefene demonstrated superiority at 5 min with an MV increase of 4.59 L/min, more than twice the 1.99 L/min increase for naloxone (P <.0001). Nalmefene superiority was also demonstrated at 10, 15, 20, and 30 min, while non‐inferiority was demonstrated at 2.5 and 90 min. The time‐course of mean antagonist concentrations correlated with increases in mean MV, peaking at approximately 5‐10 min following nalmefene compared to 20‐30 min following naloxone. Decreases in transcutaneous CO2 (TCO2) followed a similar time‐course with a slight delay. At each threshold of percent reversal (25%‐100%), nalmefene consistently showed a faster time to onset than naloxone. Both antagonist treatments were tolerated with no serious adverse events. This study shows that nalmefene 1.5 mg IM administered by auto‐injector achieved a faster onset, higher magnitude, and longer duration of reversal of OIRD compared to naloxone 4 mg IN and represents another option for the treatment of opioid overdose. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|