Nalmefene: Safety and Kinetics After Single and Multiple Oral Doses of a New Opioid Antagonist

  title={Nalmefene: Safety and Kinetics After Single and Multiple Oral Doses of a New Opioid Antagonist},
  author={Ross Dixon and Joseph A Gentile and Hon‐Bin Hsu and Jane Hsiao and John F. Howes and Dyal C. Garg and Donald Weidler},
  journal={The Journal of Clinical Pharmacology},
  • R. DixonJ. Gentile Donald Weidler
  • Published 1 March 1987
  • Medicine
  • The Journal of Clinical Pharmacology
The aim of these two studies was to evaluate the safety and pharmacokinetics of oral nalmefene, a new orally effective opioid antagonist. In the first study, single ascending doses of 50, 100, 200, and 300 mg of nalmefene HCl were administered in double‐blind fashion to four groups of healthy men. There were six subjects in each group; four received nalmefene and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, such as… 

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A double-blind, placebo-controlled study of oral nalmefene for alcohol dependence.

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A Double‐Blind, Placebo‐Controlled Pilot Study to Evaluate the Efficacy and Safety of Oral Nalmefene HCI for Alcohol Dependence

Preliminary support is provided for the hypotheses that nalmefene can be safely given to alcoholics, and that naltrexone may have a role in reducing alcohol consumption and preventing relapse, particularly at the 40 mg level.

Nalmefene: A Review of Its Use in the Treatment of Alcohol Dependence

Oral nalmefene was generally well tolerated in patients with alcohol dependence, with the most commonly occurring adverse events including nausea, insomnia and dizziness, and provides an important new option for use in the treatment of alcohol dependence.

Second generation opioidergic compounds: clinical data

The only second generation opioidergic compound for which there is substantial clinical information is nalmefene, which like naltrexone and naloxone, is a relatively non-specific opioid antagonist, binding to mu, delta, and kappa opioid receptors.

Pharmacologic and Clinical Considerations of Nalmefene, a Long Duration Opioid Antagonist, in Opioid Overdose

Nalmefene is a pure opioid antagonist structurally similar to naltrexone that can serve as an alternative antidote for reversing respiratory depression associated with acute opioid overdose and can be pivotal in reducing healthcare costs, increasing patient satisfaction, and redistributing the time that healthcare staff spend monitoring opioid overdose patients given naloxone.

Long-Term Pharmacotherapy for Opiate (Primarily Heroin) Addiction: Opioid Antagonists and Partial Agonists

Studies using naloxone showed that a specific opioid antagonist could block all exogenous opioid effects, and moreover, could reverse the effects of both exogenous and endogenous opioids.



Nalmefene: Intravenous safety and kinetics of a new opioid antagonist

In a placebo‐controlled, double‐blind study we evaluated the safety and kinetics of a new narcotic antagonist, nalmefene, after 2, 6, 12, and 24 mg intravenous doses to healthy men. At each dose

Metabolism and disposition of naltrexone in man after oral and intravenous administration.

The metabolism and elimination of [15, 16, 16,-3H2]naltrexone was studied in man after oral and intravenous administration and combined gas chromatography-mass spectrometry was used to validate the presence of nALTrexone, 6 beta-nALTrexol, and 2-hydroxy-3-O-methyl-6 beta- naltrexol in urine.

Prolonged blockade of opioid effect with oral nalmefene

It is suggested that nalmefene could provide prolonged effectiveness in limiting emergence of opioid effects during addiction therapy and good oral bioavailability and a prolonged terminal elimination phase.

Nalmefene: radioimmunoassay for a new opioid antagonist.

The use of the RIA for the pharmacokinetic evaluation of nalmefene is illustrated with plasma concentration profiles of the drug in humans following intravenous and oral administration.

Binding of a new opiate antagonist, nalmefene, to rat brain membranes.

Results indicate that nalmefene is a universal opiate antagonist, has no agonist character at the central mu site and binds more effectively to central opiate receptors than either naloxone or naltrexone.

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The majority of the new narcotic antagonists exhibited oral potencies considerably superior to the parent compounds, with 6-methylene derivatives IIa and IIb showing the most impressive increases.

Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration.

There was excellent linearity between the administered dose and the area under the plasma concentration-time profile, as well as total urinary recovery of both drug and metabolite.