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.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2009年第16期1366-1369,共4页
Chinese Journal of Hospital Pharmacy
