Time Course of Reversal of Fentanyl‐Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene and Intramuscular and Intranasal Naloxone.
The increase in opioid overdose deaths, particularly involving potent, long‐acting synthetic opioids, has led to calls for stronger, longer‐acting opioid‐overdose‐reversal agents. Using an opioid‐induced respiratory depression model, we investigated the onset and time course of action of naloxone an...
| Publicado en: | Journal of Clinical Pharmacology Vol. 65; no. 2; pp. 206 - 217 |
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| Autores principales: | , , , , , |
| Formato: | research tables/charts randomized controlled trial Journal Article |
| Publicado: |
Wiley-Blackwell
Feb2025
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| 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=183981163&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 183981163 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00912700 5WH jtl: Journal of Clinical Pharmacology issn: 00912700 maglogo: Y pubinfo: dt: Feb2025 vid: 65 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 183981163 180029378 183981163 183981163 10.1002/jcph.6132 183981163 ppf: 206 ppct: 11 formats: tig: atl: Time Course of Reversal of Fentanyl‐Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene and Intramuscular and Intranasal Naloxone. aug: au: Cipriano, Alessandra Apseloff, Glen Kapil, Ram P. He, Ellie Shet, Manjunath Harris, Stephen C. affil: Imbrium Therapeutics L.P., a subsidiary of Purdue Pharma L.P., Stamford CT,, USA sug: subj: Fentanyl Adverse Effects Respiration Disorders Chemically Induced Respiration Disorders Drug Therapy Narcotic Antagonists Administration and Dosage Naloxone Administration and Dosage Injections, Intramuscular Administration, Intranasal Time Drug Efficacy Evaluation Narcotic Antagonists Pharmacokinetics Naloxone Pharmacokinetics Patient Safety Evaluation Fentanyl Administration and Dosage Drug Therapy, Combination Human Male Female Adolescence Adult Middle Age Funding Source Randomized Controlled Trials Crossover Design Random Assignment Comparative Studies Narcotic Antagonists Blood Narcotic Antagonists Adverse Effects Naloxone Adverse Effects Prospective Studies Narcotic Antagonists Pharmacodynamics Naloxone Pharmacodynamics Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Male Female ab: The increase in opioid overdose deaths, particularly involving potent, long‐acting synthetic opioids, has led to calls for stronger, longer‐acting opioid‐overdose‐reversal agents. Using an opioid‐induced respiratory depression model, we investigated the onset and time course of action of naloxone and a long‐acting opioid antagonist, nalmefene, in reversing the effects of an ongoing intravenous fentanyl infusion over a period of up to 100 min. Healthy, moderately experienced opioid users received intramuscular (IM) nalmefene 1 mg, IM naloxone 2 mg, or intranasal (IN) naloxone 4 mg after fentanyl‐induced respiratory depression was established based on reduction in respiratory minute volume (MV). Each participant received each opioid antagonist twice per a randomized crossover schedule. Reversal of respiratory depression, pharmacokinetics, and safety were investigated. Participants showed rapid increases in plasma opioid antagonist concentrations, and meaningful reversal of depressed MV tended to occur earlier with IM nalmefene and IM naloxone than with IN naloxone. Compared to naloxone, nalmefene provided extended exposure, and mean MV was maintained at a higher level. All participants experienced treatment‐related adverse events, but none were severe, serious, or led to study drug discontinuation. This study provides evidence that IM nalmefene 1 mg achieves reversal of fentanyl‐induced respiratory depression similar to or better than that achieved with standard‐of‐care naloxone treatments. No new safety concerns were raised for IM nalmefene at the tested dose. The pharmacokinetic and pharmacodynamic properties of IM nalmefene position it as an important treatment option in opioid overdose reversal, particularly given the increasing prevalence of overdoses involving potent, long‐acting synthetic opioids. pubtype: Academic Journal doctype: research tables/charts randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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