盐酸纳美芬注射液在健康人体中的药动学研究

Pharmacokinetics of Intravenous Nalmefene in Healthy Volunteers

目的研究中国健康志愿者单剂量静脉推注0.25、0.5、1.0μg.kg-1盐酸纳美芬注射液后的药动学行为,并评价药动学参数在0.25～1.0μg.kg-1内剂量相关性。方法 12名健康志愿者,随机三交叉试验,分别单剂量静脉推注盐酸纳美芬注射液0.25、0.5、1.0μg.kg-1;测定给药后48 h内的血药浓度。结果单剂量静脉推注0.25、0.5、1.0μg.kg-1盐酸纳美芬注射液后,纳美芬的消除半衰期大约为13～15 h,血浆药物浓度(ρmax)随剂量增加呈线性增加[(104.4±61.9)～(330.6±152.5)pg.mL-1]。另外,曲线下面积(AUC)在0.25～1.0μg.kg-1内也呈线性增加[AUC0-t(301.4±86.8)～(1 023.1±214.2)pg.h.mL-1,AUC0-∞:(337.1±82.7)～(1 115.2±302.3)pg.h.mL-1]。结论在0.25～1.0μg.kg-1内纳美芬呈线性药动学,ρmax、AUC的升高与剂量成正比。tmax、t1/2、AUC0-t、CL/F、Vd/F性别间无统计学差异,但是ρmax有明显统计学差异。

OBJECTIVE To characterize the pharmacokinetics of a single dose of nalmefene injection at doses of 0.25,0.5,1.0 μg·kg-1 in healthy subjects,and assess the dose proportionality of nalmefene over the potential therapeutic dose range（0.25-1.0 μg·kg-1）.METHODS In a randomized three-way crossover study,twelve healthy subjects received a single dose of intravenous injection at the doses of 0.25,0.5,1.0 μg·kg-1 nalmefene.Plasma concentrations were determined at selected time intervals for 48 h.RESULTS The elimination half-life of nalmefene after i.v 0.25,0.5,1.0 μg·kg-1 nalmefene was about 13-15 h,the peak plasma concentration（ρmax） was increased linearly from（104.4±61.9） pg·mL-1 to（330.6±152.5） pg·mL-1 with the increasing dose.Moreover,the area under the plasma concentration vs time curve was increased linearly within the dose range of 0.25-1.0 μg·kg-1 [AUC0-t from（301.4±86.8） pg·h·mL-1 to（1 023.1±214.2） pg·h·mL-1,AUC0-∞ from（337.1±82.7） pg·h·mL-1 to（1 115.2±302.3） pg·h·mL-1].CONCLUSION Nalmefene exhibits a linear pharmacokinetic profile in the dose range of 0.25-1.0 μg·kg-1.Dose-dependent parameters（ρmax and AUC）showed an approximately dose-dependented manner from 0.25 μg·kg-1 to 1.0 μg·kg-1.The differences of the pharmacokinetic parameters（tmax,t1/2,AUC0-t,CL/F and Vd/F） between genders were not statistically significant,but difference of ρmax was statistically significant.