阿立哌唑片在中国健康受试者中的生物等效性研究  

Bioequivalence study of aripiprazole tablets in Chinese healthy subjects

作　　者：王蕊[1] 孟现民[2] 唐代茂 WANG Rui;MENG Xian-min;TANG Dai-mao(Department of Clinical Medicine,Nhwa Pharmaceutical Co.Ltd.,Xuzhou 221007,Jiangsu Province,China;Shanghai Public Health Clinical Center,Shanghai 201508,China)

机构地区：[1]江苏恩华药业股份有限公司临床医学部,江苏徐州221007 [2]上海市公共卫生临床中心,上海201508

出　　处：《中国临床药理学杂志》2023年第1期91-96,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的评价2种阿立哌唑片在中国健康受试者中空腹和餐后状态下给药的生物等效性及安全性。方法采用单中心、随机、开放、两制剂、两周期、交叉试验设计,共纳入72例受试者(空腹试验36例,餐后试验36例),受试者每周期空腹或餐后单次口服阿立哌唑片受试制剂和参比制剂10 mg,清洗期42 d。应用HPLC-MS/MS法测定人血浆中阿立哌唑浓度,用WinNonlin 8.1并用非房室模型计算药代动力学参数,进行等效性评价。结果空腹试验中服用受试制剂和参比制剂阿立哌唑的主要药代参数:C_(max)分别为(49.02±13.32),(50.26±10.71)ng·mL^(-1),AUC_(0-72 h)分别为(1622.75±355.06),(1672.52±346.96)h·ng·mL^(-1),AUC_(0-∞)分别为(3501.12±2064.98),(3291.13±1312.20)h·ng·mL^(-1),T_(max)分别为2.25(1.00~7.00),2.00(1.00~8.00)h,Cmax、AUC_(0-72 h)、AUC_(0-∞)的几何均值比值的90%置信区间分别为92.78%~100.58%、94.16%~99.83%、90.95%~109.16%。餐后试验中服用受试制剂和参比制剂阿立哌唑的主要药代参数:C_(max)分别为(44.60±7.03),(45.60±9.74)ng·mL^(-1),AUC_(0-72 h)分别为(1725.95±317.23),(1759.26±382.60)h·ng·mL^(-1),AUC_(0-∞)分别为(3348.54±1050.88),(3574.46±1406.78)h·ng·mL^(-1),T_(max)分别为4.50(2.50~24.00),4.50(3.00~24.00)h,C_(max)、AUC_(0-72 h)、AUC_(0-∞)的几何均值比值的90%置信区间分别为97.11%~108.11%、95.74%~101.66%、89.01%~102.07%。在空腹和餐后条件下,受试制剂和参比制剂主要药代参数90%置信区间均落在生物等效性的范围内(80%~125%)。空腹和餐后试验期间均未发生严重药物不良反应。结论阿立哌唑片受试制剂和参比制剂在健康受试者空腹/餐后状态下具有生物等效性,具有较好的安全性。Objective To evaluate the bioequivalence and safety of two kinds of aripiprazole tablets administration under fasting and fed conditions in Chinese healthy subjects.Methods This was a singlecenter,randomized,open-lable,two preparations,two periods,crossover design.A total of 72 subjects(36 subjects in fasting and 36 subjects in fed conditions)were given single oral dose 10 mg of the test and reference preparations of aripiprazole tablets.The concentrations of aripiprazole in plasma were determined by the HPLC-MS/MS method.The pharmacokinetic parameters and bioequivalence were evaluated by non-compartment model of WinNonlin 8.1.Results The main pharmacokinetic parameters of aripiprazole after taking the test and reference preparations were as follows:In fasting conditions,Cmaxwere(49.02±13.32)and(50.26±10.71)ng·mL^(-1),AUC0-72 hwere(1622.75±355.06)and(1672.52±346.96)h·ng·mL^(-1),AUC0-∞were(3501.12±2064.98)and(3291.13±1312.20)h·ng·mL^(-1),T_(max)were 2.25(1.00-7.00)and 2.00(1.00-8.00)h,the 90%confidence interval of C_(max),AUC_(0-72h)and AUC_(0-∞) geometric mean ratio were 92.78%-100.58%,94.16%-99.83%,90.95%-109.16%;in fed conditions,Cmaxwere(44.60±7.03)and(45.60±9.74)ng·mL^(-1),AUC_(0-72h) were(1725.95±317.23)and(1759.26±382.60)h·ng·mL^(-1),AUC_(0-∞) were(3348.54±1050.88)and(3574.46±1406.78)h·ng·mL^(-1),T_(max) were 4.50(2.50-24.00)and 4.50(3.00-24.00)h,the 90%confidence interval of C_(max),AUC_(0-72h) and AUC_(0-∞) geometric mean ratio were 97.11%-108.11%,95.74%-101.66%,89.01%-102.07%.Under both conditions,the 90% confidence interval of the main pharmacokinetic parameters of the test and reference preparations were between 80% and 125% which met the criteria for bioequivalence evaluation.No serious adverse drug reactions occurred during the fasting and fed study.Conclusion Under the fasting and fed conditions,the test and reference preparations of aripiprazole tablets were bioequivalent in healthy subjects and had good safety.

关 键 词：阿立哌唑 生物等效性 药代动力学 液质联用技术 

分 类 号：R97[医药卫生—药品]