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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 study the pharmacokinetics of nalmefene hydrochloride 0.25, 0.5, 1.0 μg.kg-1 nalmefene hydrochloride injection in healthy volunteers in China and to evaluate the pharmacokinetic parameters in the range of 0.25-1.0 μg.kg-1 Dose-related. Methods Twelve healthy volunteers were randomized to three-crossover trials. One single dose of nalmefene hydrochloride injection 0.25, 0.5, and 1.0 μg · kg-1 respectively. The plasma concentrations were measured within 48 hours after administration. Results After single-dose intravenous injection of nalmefene hydrochloride 0.25, 0.5, 1.0 μg.kg-1, the elimination half-life of nalmefene was about 13-15 h. The plasma drug concentration (ρmax) increased linearly with dose (104.4 ± 61.9) ~ (330.6 ± 152.5) pg.mL-1]. In addition, the area under the curve (AUC) also increased linearly from 0.25 to 1.0 μg · kg-1 [AUC0-t (301.4 ± 86.8) ~ (1023.1 ± 214.2) pg.h.mL- (337.1 ± 82.7) ~ (115.2 ± 302.3) pg.h.mL-1]. Conclusions Nalmefene is linear pharmacokinetic in the range of 0.25-1.0 μg.kg-1. The increase of ρmax and AUC is proportional to the dose. There was no significant difference between tmax, t1 / 2, AUC0-t, CL / F and Vd / F gender, but there was a significant difference in ρmax.