氯氮平片在中国精神分裂症患者中的生物等效性研究  

Study on bioequivalence of clozapine tablets in patients with schizophrenic in China

作　　者：董芳 李安宁[1,2] 史犇 朱雪泉 翟屹民 袁晓菲 田腾飞 张志洋 姜涛 DONG Fang;LI An-ning;SHI Ben;ZHU Xue-quan;ZHAI Yi-min;YUAN Xiao-fei;TIAN Teng-fei;ZHANG Zhi-yang;JIANG Tao(The National Clinical Research Center for Mental Disorders,Beijing Anding Hospital,Capital Medical University,Beijing Key Laboratory of Mental Disorders,Beijing Institute for Brain Disorders Center of Schizophrenia,Beijing 100088,China;Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing 100069;Suzhou Guochen Biotek Company Limited,Suzhou 215000,Jiangsu Province,China)

机构地区：[1]首都医科大学附属北京安定医院国家精神心理疾病临床医学研究中心、精神疾病诊断与治疗北京市重点实验室、北京脑重大疾病研究院精神分裂症研究所,北京100088 [2]首都医科大学人脑保护高精尖创新中心,北京100069 [3]苏州国辰生物科技股份有限公司,江苏苏州215000

出　　处：《中国临床药理学杂志》2020年第16期2486-2489,共4页The Chinese Journal of Clinical Pharmacology

基　　金：重大新药创制精神性疾病示范性新药临床评价技术平台建设基金资助项目(2018ZX09201-014);国家自然科学基金青年科学基金项目(81801322);北京市医院管理局临床医学发展专项“杨帆”计划重点医学专业精神分裂症专业基金资助项目(ZYLX201807)。

摘　　要：目的评价2种氯氮平片在中国精神分裂症患者体内的生物等效性及安全性。方法采用单中心、开放、随机、双周期交叉、自身对照设计方法,共入组患者44例,随机交叉连续口服可变剂量(维持入组前所服用剂量)的受试药物和参比药物各10 d,用LC-MS/MS法测定血浆中氯氮平的血浆浓度,用WinNonlin7.0版本软件,计算氯氮平剂量标准化后的药代动力学参数,并进行生物等效性评价。结果患者连续服用受试药物和参比药物达稳态后,空腹服药状态下,血浆中氯氮平经25 mg剂量标准化后的主要药代动力学参数如下:Cmax分别为(166.20±54.70) ng·mL-1,(159.07±53.90) ng·mL-1;AUC0-t分别为(1363.48±470.94) ng·mL-1·h,(1325.15±514.81) ng·mL-1·h。2种制剂的Cmax和AUC0-t经对数转换后90%可信区间分别为90.84%~100.87%,92.93%~99.26%。结论 2种氯氮平片在中国精神分裂症患者中具有生物等效性。Objective To evaluate the bioequivalence of two clozapine tablets in patients with schizophrenic. Methods This was a single-center, open-label, randomized, two-period, cross-over pharmacokinetic study. And 44 patients were given individualized oral dose(the same dose using before they took part in the study) of test and reference preparation of clozapine tablets for 10 days respectively. The concentration of clozapine in patients’ plasma was measured by LC-MS/MS. Main pharmacokinetic parameters were calculated by using WinNonlin 7.0 software and bioequivalence was evaluated. Results The main pharmacokinetic parameters of clozapine normalized to a 25 mg dose of the test and reference preparations were as follows: Cmax were(166.20±54.70) ng·mL-1,(159.07±53.90) ng·mL-1;AUC0-t were(1363.48±470.94) ng·mL-1·h,(1325.15±514.81) ng·mL-1·h. The 90% confidential interval of Cmax and AUC0-t of tested formulation were 90.84%-100.87% and 92.93%-99.26%. Conclusion Two kinds of clozapine tablets are bioequivalent in patients with schizophrenic in China.

关 键 词：氯氮平 精神分裂症 生物等效性 

分 类 号：R97[医药卫生—药品]