摘要
目的:研究福多司坦片在中国健康志愿者体内单次及多次给药的药动学特征。方法:选择健康受试者12例,单次给药按3×3拉丁方设计,分别交叉口服福多司坦片200,400,600mg,多次给药按每天给药3次,每次400mg,连续给药4d,采用LC-MS测定不同时间点血中福多司坦片的浓度,在计算机上以DAS2.0软件进行数据处理,计算药动学参数。结果:受试者单次口服福多司坦片200,400,600mg后,3个不同剂量组福多司坦的主要药动学参数Cmax分别为(8.8±4.2),(19.4±4.0),(33.6±11.5)mg·L-1,AUC0-t分别为(15.6±3.7),(30.4±6.5),(55.3±9.0)mg·h·L-1,tmax分别为(0.44±0.15),(0.5±0.3),(0.46±0.12)h,t1/2分别为(3.1±0.6),(3.0±0.5),(2.6±0.3)h;CL/F分别为(12.7±3.2),(12.5±2.4),(10.7±1.7)h-1;单次给药各剂量组的Cmax、AUC0-t、AUC0-∞随着剂量的增加成比例增大,各组的tmax、Ke、t1/2、MRT、CL/F等药动学参数差异无统计学意义。受试者连续多次口服福多司坦片400mg后,其Cmax、AUC0-t、AUC0-∞分别为(18.7±5.8)mg·L-1、(29.3±11.0)mg·h·L-1和(31.1±11.9)mg·h·L-1,t1/2为(3.1±0.5)h,与单次给药400mg的药动学参数相比,差异无显著性。结论:口服给药剂量范围为200～600mg时,福多司坦在国人体内具有线性药动学特征;福多司坦片按每日给药3次,每次口服400mg,在国人体内不会产生蓄积现象。
OBJECTIVE To investigate the pharmacokinetics of single dose and multiple dose of fudosteine tablets in chinese healthy volunteers. METHODS 12 volunteers were divided into three groups and fudosteine concentrations in plasma of 12 volunteers after taking 200, 400 and 600 mg fudosteine and taking multiple 400 mg fudosteine were determined by LC-MS. The pharmacokinetic parameters were calculated by DAS 2. 0 software. RESULTS The main pharmacokinetics parameters of single dose： Cmax were 8. 8 ± 4. 2, 19. 4± 4. 0 and 33.6 ± 11.5 mg·L^-1, respectively; AUC0-t, were 15.6 ± 3.7,30. 4 ± 6. 5and 55.3 ± 9. 0 mg·h·L^-1, respectively; tmax were 0. 44 ± 0. 15, 0. 54 ± 0. 34 and 0. 46 ± 0. 12 h, respectively; t1/2 were 3.1 ± 0. 6,3.0 ± 0. 5 and 2. 65 ± 0.33 h, respectively,CL/F were 12.7 ± 3.2,12. 5 ± 2. 4 and 10. 7 ± 1.7 h^-1, respectively. The main pharmacokinetics parameters Cmax. AUC0-t, AUC0-∞ showed direct proportion to doses. There were no singnificant difference in tmax, t1/2 , MRT and CL/F of three groups. The parameters of multiple dose： Cmax was 18.7 ± 5.8 mg·L^-1 ; AUC0-t, and AUC0-∞ were 29. 3 ± 11.0 mg· h·L^-1 and 31.1 ± 11.9 mg· h·L^-1, respectively; t1/2 was 3. 1± 0. 5 h; Cmax was 2. 4 ± 0. 9 mg · L^-1; and DF% was （7. 8 ± 2. 2）%. CONCLUSION The pharmacokinetics of fudosteine between 200 mg and 600 mg in human body was linear. There was no drug accumulation after taking multiple dose.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2008年第16期1370-1373,共4页
Chinese Journal of Hospital Pharmacy
作者简介
张红，女，硕士，讲师，电话：0791-6360654
[通讯作者]熊玉卿，博士生导师，电话：0791-6361114
