盐酸纳美芬注射液在健康人体中的药动学研究

 目的 研究中国健康志愿者单剂量静脉推注0.25、0.5、1.0 μg·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0.25~1.0 μg·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、1.0 μg·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、1.0 μg·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(ρ_max)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0.25~1.0 μg·kg-1内也呈线性增加AUC_0-t（301.4±86.8）~（1 023.1±214.2）pg·h·mL-1, AUC_0-∞：（337.1±82.7）~（1 115.2±302.3） pg·h·mL-1]。结论 在0.25~1.0 μg·kg-1内纳美芬呈线性药动学，ρ_max、AUC的升高与剂量成正比。t_max、t1/2、AUC_0-t、CL/F、V_d/F性别间无统计学差异，但是ρ_max有明显统计学差异。

Pharmacokinetics of Intravenous Nalmefene in Healthy Volunteers

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 (ρ_max) 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 AUC_0-t from （301.4±86.8） pg·h·mL-1 to （1 023.1±214.2） pg·h·mL-1, AUC_0-∞ 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（ρ_max 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 (t_max， t1/2， AUC_0-t， CL/F and V_d/F) between genders were not statistically significant, but difference of ρ_max was statistically significant.