健康志愿者口服依托度酸缓释片的药动学及生物等效性  

Pharmacokinetics and bioequivalence of etodolac sustained released tablets in healthy volunteers

作　　者：黄竞[1] 吴晨[1] 杨丽[1] 严宝霞[1] 

机构地区：[1]北京大学第三医院,北京100083

出　　处：《中国医院药学杂志》2003年第9期519-521,共3页Chinese Journal of Hospital Pharmacy

摘　　要：目的 :建立依托度酸的血药浓度测定方法 ,研究国产受试制剂与进口参比制剂在健康人体内的药动学特征及其生物等效性。方法 :2 0名健康男性志愿者多剂量交叉口服依托度酸缓释片受试制剂和参比制剂 ,采用HPLC法测定血浆中依托度酸的浓度 ,计算药动学参数和相对生物利用度 ,并对所得参数进行方差分析和双单侧t检验。结果 :依托度酸缓释片受试制剂及参比制剂的主要药动学参数为 :Cssmax分别为 (11.2± 3.7)mg·L-1和 (12 .0± 4 .4 )mg·L-1;Cssmin分别为 (4 .5± 2 .1)mg·L-1和 (4 .4± 1.6 )mg·L-1;稳态平均血药浓度Cav分别为 (5 .9± 2 .4 )mg·L-1和 (6 .2± 1.9)mg·L-1;血药浓度波动系数DF(% )分别为 (12 8.4± 6 7.4 ) %和 (131.2± 5 3.7) % ;Tssmax分别为 (2 .0± 1.5 )h和 (4 .0± 2 .7)h ;t1/ 2 分别为 (14 .1± 2 .1)h和 (13.4±2 .3)h ;稳态条件下AUCss0→ 2 4分别为 (14 1.± 5 7.2 )mg·L-1·h-1和 (14 6 .3± 4 4 .6 )mg·L-1·h-1;稳态条件下的相对生物利用度F(0→ 2 4) 为 (98.8± 32 .1) %。结论 :经统计学分析 。OBJECTIVE To develop an HPLC method to determine the concentration of etodolac in human plasma and study its pharmacokinetic profile and bioequivalence using an import preparation as reference. METHODS Multi oral dose ( 400 mg ) of the test and reference etodolac sustained released tablets were given to 20 healthy male volunteers in a randomized cross over study. The concentrations in plasma were determined by HPLC. The pharmacokinetic parameters and relative bioavailability were calculated. Variance analysis and two one sided test statistical analysis were performed for pharmacokinetic parameters.RESULTS The main pharmacokinetic parameters of the two etodolac sustained released tablets were as follows: C max were ( 11.2 ± 3.7) mg ·L -1 and ( 12.0 ± 4.4) mg ·L -1 ; C min were (4.5 ± 2.1) mg ·L -1 and ( 4.4 ± 1.6) mg ·L -1 ;average plasma concentration C av were ( 5.9 ± 2.4) mg ·L -1 and (6.2 ± 1.9) mg ·L -1 ;DF(%) were ( 128.4 ± 67.4)% and ( 131.2 ± 53.7)% ; T ss max were ( 2.0 ± 1.5) h and ( 4.0 ± 2.7) h ; t 1/2 were ( 14.1 ± 2.1) h and ( 13.4 ± 2.3) h ;AUC ss 0→24 were ( 141.6 ± 57.2) mg ·L -1 ·h -1 and ( 146.3 ± 44.6) mg ·L -1 ·h -1 ;The relative bioavailability of AUC ss 0→24 were ( 98.8 ± 32.1)% ?CONCLUSIONS The result of statistical analysis showed the two formulations were bioequivalent.

关 键 词：依托度酸缓释片 生物等效性 药动学 高效液相色谱法 测定 

分 类 号：R969[医药卫生—药理学] R971.1[医药卫生—药学]