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 t1/2 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 t1/2, and AUC showed no consistent 
trends related to increasing doses, indicating that nalmefene has linear 
pharmacokinetics.