Dixon R, Howes J, Gentile J, Hsu H B, Hsiao J, Garg D, Weidler D, Meyer M, Tuttle R
Clin Pharmacol Ther. 1986 Jan;39(1):49-53. doi: 10.1038/clpt.1986.9.
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.
在一项安慰剂对照的双盲研究中，我们评估了一种新型麻醉拮抗剂纳美芬对健康男性静脉注射2毫克、6毫克、12毫克和24毫克剂量后的安全性和动力学。在每个剂量水平，四名受试者接受活性药物，两名受试者接受安慰剂。该药物在所有剂量水平下耐受性良好，仅出现轻微和短暂的副作用，最常见的是头晕。血浆浓度-时间数据最适合用三指数方程拟合，终末消除相的调和平均t1/2为8至9小时。仅约5%的剂量以完整的纳美芬形式经尿液排泄，高达60%以纳美芬葡萄糖醛酸苷形式排泄。尽管观察到个体间差异，但平均或剂量标准化的平均动力学参数，如清除率、稳态分布容积、终末t1/2和AUC，未显示出与剂量增加相关的一致趋势，表明纳美芬具有线性药代动力学。
