阿片类拮抗药纳美芬注射剂的单剂量和多剂量I期临床药代动力学研究  

Pharmacokinetics of nalmefene after a single or multiple intravenous doses in Chinese healthy volunteers

作　　者：廖日房[1] 曾转萍[2] 温预关[3] 

机构地区：[1]中山大学附属第二医院临床药学部,广东广州510120 [2]广东药学院流行病与卫生统计教研室,广东广州510315 [3]广州市脑科医院临床药理研究所,广东广州510520

出　　处：《南方医科大学学报》2008年第10期1816-1819,共4页Journal of Southern Medical University

基　　金：广东省自然科学基金(8151037001000001);广东省医学科学技术研究基金(A2008559);广州市医药卫生科技计划(2007-YB-106)

摘　　要：目的考察静脉推注盐酸纳美芬注射液后在健康人体内的药动学过程。方法12名健康受试者随机交叉单剂量静脉推注给药2mg后,分别于给药前和给药后5min,0.25,0.5,1,1.5,2,2.5,3,4,6,8,12,24,36和48h采集血样,单剂量试验结束后进入多剂量试验,8名受试者静脉推注给药2mg,连续给药6d,并于给药后的第4,5,6天早上给药前采静脉血,于第6天给药后按设定时间点采集血样,用高效液相色谱-质谱法测定血浆中纳美芬的浓度,并采用PKS药动学程序对试验数据进行处理,求算有关药动学参数。结果单剂量静脉推注盐酸纳美芬注射液2mg后,其药-时曲线经拟合符合二室模型,12名健康受试者单剂量给药后其主要药动学参数Cmax,Tmax,T1/2,AUC0-48,AUC0-∞分别为(7.34±1.56)μg·L-1,0.08h,(12.01±2.20)h,(30.29±9.84)μg·L-1·h,(32.23±9.94)μg·L-1·h,多次静脉推注2mg后的主要药动学参数Cmax,Tmax,T1/2,AUC0-48,AUC0-∞分别(8.04±1.09)μg·L-1、0.08h、(12.43±1.44)h、(33.64±9.15)μg·L-1·h和(35.98±9.23)μg·L-1·h,血药浓度波动系数、AUCss和Cav分别为(4.69±1.29)、(19.64±6.20)μg·L-1·h和(1.64±0.52)μg·L-1。结论盐酸纳美芬注射液单剂量静脉推注2mg和多次给药2mg后人体内的药动学行为与国外文献报道基本一致。在连续多次给药时,并未出现蓄积现象,血药浓度第6天达稳态。Objective To investigate the pharmacokinetics of nalmefene after intravenous administration at a single or multiple doses in Chinese healthy volunteers. Methods This open, randomized clinical trial involved 12 healthy volunteers, who received a single-dose （2 mg） nalmefene injection. Before and at different time points after the injection, blood sample were obtained from the subjects. After the single intravenous dose trial, 8 healthy volunteers received intravenous nalmefene at 2 mg once daily for 6 consecutive days, and the plasma drug concentrations were determined on the morning of days 4, 5 and 6 using liquid chromatograpy/tandem mass spectrometry and the pharmacokinetic parameters were calculated using PKS program. Results The main pharmacokinetic parameters of nalmefene （Cmax,Tmax,T1/2,AUC0.48,and AUC0-∞） after the single intravenous dose were （7.34±1.56）μg·L^-1,0.08h,（12.01±2.20）h,（30.29±9.84）μg·L^-1·h,and （32.23±9.94）μg·L^-1.h, respectively; the parameters after multiple doses were （8.04＋1.09）μg·L^-1、0.08h、（12.43±1.44）h、（33.64±9.15）μg·L^-1·h and（35.98±9.23）μg·L^-1·h, respectively. The steady-state pharmacokinetic parameters including the degree of fluctuation （DF）, AUCss and Cav were（4.69±1.29）、（19.64±6.20）μg·L^-1·h and（1.64±0.52）μg·L^-1, respectively. Conclusion Nalmefene showed similar pharmacokinetics in Chinese healthy volunteers with those in the foreign testees, and can be safely administered in healthy volunteers without producing unmanageable pain.

关 键 词：纳美芬 药代动力学 高效液相色谱法 

分 类 号：R969.1[医药卫生—药理学] R971.6[医药卫生—药学]