氯氮平分散片人体生物等效性研究  

Study on bioequivalence of clozapine dispersible tablets in healthy volunteers

作　　者：刘宪勇[1,2] 王本杰[3] 魏春敏[3] 袁桂艳[3] 李荣[3] 郭瑞臣[3] 

机构地区：[1]山东大学药学院,山东济南250012 [2]武警山东总队医院,山东济南250014 [3]山东大学齐鲁医院,山东济南250012

出　　处：《中国医院药学杂志》2009年第16期1366-1369,共4页Chinese Journal of Hospital Pharmacy

摘　　要：目的:进行受试制剂氯氮平分散片与市售参比制剂氯氮平片人体生物等效性研究。方法:采用2周期交叉试验设计。健康志愿者分别服用受试制剂或参比制剂,于给药前和给药后0.5,1,1.5,2,2.5,3,3.5,4,5,8,12,24,36,48h取肘静脉血4mL,以米氮平为内标,采用高效液相色谱-质谱法测定氯氮平血药浓度。采用DAS2.0程序求算氯氮平主要药动学参数,评价两制剂的生物等效性。结果:氯氮平受试制剂和参比制剂主要药动学参数t1/2为(14.0±4.0)h和(14.6±3.7)h,tmax为(2.4±0.8)h和(2.3±0.5)h,Cmax为(138.2±53.0)μg.L-1和(138.9±46.5)μg.L-1,AUC0-48为(1 822.9±580.0)μg.L-1.h和(1 848.4±575.0)μg.L-1.h,AUC0～∞为(2 031.7±705.3)μg.L-1.h和(2 063.2±668.2)μg.L-1.h。氯氮平分散片相对生物利用度F为(99.1±11.0)%。结论:受试制剂与参比制剂主要药动学参数差异无显著性,为生物等效制剂。OBJECTIVE To investigate the bioequivalence of clozapine dispersible tablets and clozapine tablets in healthy volunteers, METHODS Twenty healthy volunteers were orally given with clozapine dispersible tablets and clozapine tablets in a two period cross test design, and blood was collected before and after 0.5, 1, 1.5,2, 2. 5,3, 3. 5, 4, 5, 8, 12, 24,36 h and 48 h. Plasma were removed and clozapine in plasma were determined by HPLC/MS method with mirtazapine as internal standard. The main pharmaeokinetics parameters of clozapine were calculated and the bioequivalence of two preparations was evaluated. RESULTS The main pharmacokinetics parameters of clozapine dispersible tablets and elozapine tablets were as follows： t1/2 （14. 0 ± 4. 0）h and （14. 6 ± 3.7）h,tmax（2. 4 ± 0. 8）h and （2.3 ± 0. 5）h,Cmax（138. 2 ± 53.0）μg.L^-1 and （138. 9 ± 46. 5）μg·L^-1 ,AUG0-48 （ 1 822. 9 ± 580. 0） μg· L^-1·h and （ 1 848. 4 ± 575.0） μg· L^-1·h, AUG0→∞ （ 2 031.7 ± 705.3 ） μg · L^-1· h and （ 2 063.2 ± 668. 2）μg·L^-1·h. CONCLUSION There are no significant differences between clozapine pharmacokinetics parameters of dis persible tablets and common tablets, and two preparations are bioequivalent.

关 键 词：氯氮平 米氮平 生物等效性 高效液相色谱-质谱法 

分 类 号：R969[医药卫生—药理学]