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Nalmefene: Intravenous safety and kinetics of a new opioid antagonist
Author(s) -
Dixon Ross,
Howes John,
Gentile Joseph,
Hsu HonBin,
Hsiao Jane,
Garg Dyal,
Weidler Donald,
Meyer Marvin,
Tuttle Ronald
Publication year - 1986
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1986.9
Subject(s) - nalmefene , pharmacokinetics , volume of distribution , pharmacology , placebo , medicine , narcotic antagonist , lightheadedness , anesthesia , antagonist , naltrexone , chemistry , receptor , alternative medicine , pathology
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 level four subjects received active drug and two received placebo. The drug was well tolerated at all dose levels with only mild and transient side effects, the most common of which was lightheadedness. The plasma concentration‐time data were best fit with a triexponential equation, and the terminal elimination phase had a harmonic mean t 1/2 of 8 to 9 hours. Only about 5% of the dose was excreted in the urine as intact nalmefene, with up to 60% excreted as nalmefene glucuronide. Although intersubject differences were noted, mean or dose‐normalized mean kinetic parameters such as clearance, steady‐state volume of distribution, terminal t 1/2 , and AUC showed no consistent trends related to increasing doses, indicating that nalmefene has linear pharmacokinetics. Clinical Pharmacology and Therapeutics (1986) 39, 49–53; doi: 10.1038/clpt.1986.9